Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-01-04

AUTHORS

Diana L. Cousminer, Yadav Wagley, James A. Pippin, Ahmed Elhakeem, Gregory P. Way, Matthew C. Pahl, Shana E. McCormack, Alessandra Chesi, Jonathan A. Mitchell, Joseph M. Kindler, Denis Baird, April Hartley, Laura Howe, Heidi J. Kalkwarf, Joan M. Lappe, Sumei Lu, Michelle E. Leonard, Matthew E. Johnson, Hakon Hakonarson, Vicente Gilsanz, John A. Shepherd, Sharon E. Oberfield, Casey S. Greene, Andrea Kelly, Deborah A. Lawlor, Benjamin F. Voight, Andrew D. Wells, Babette S. Zemel, Kurt D. Hankenson, Struan F. A. Grant

ABSTRACT

BackgroundBone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype by modeling longitudinal bone accrual across 11,000 bone scans in a cohort of healthy children and adolescents, followed by genome-wide association studies (GWAS) and variant-to-gene mapping with functional follow-up.ResultsWe identify 40 loci, 35 not previously reported, with various degrees of supportive evidence, half residing in topological associated domains harboring known bone genes. Of several loci potentially associated with later-life fracture risk, a candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3). Variant-to-gene mapping combining ATAC-seq to assay open chromatin with high-resolution promoter-focused Capture C identifies contacts between GWAS loci and nearby gene promoters. siRNA knockdown of gene expression supports the putative effector gene at three specific loci in two osteoblast cell models. Finally, using CRISPR-Cas9 genome editing, we confirm that the immediate genomic region harboring the putative causal SNP influences PRPF38A expression, a location which is predicted to coincide with a set of binding sites for relevant transcription factors.ConclusionsUsing a new longitudinal approach, we expand the number of genetic loci putatively associated with pediatric bone gain. Functional follow-up in appropriate cell models finds novel candidate genes impacting bone accrual. Our data also raise the possibility that the cell fate decision between osteogenic and adipogenic lineages is important in normal bone accrual. More... »

PAGES

1

References to SciGraph publications

  • 2000-11. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ in NATURE
  • 2016-06-13. A splicing isoform of TEAD4 attenuates the Hippo–YAP signalling to inhibit tumour proliferation in NATURE COMMUNICATIONS
  • 2017-01-13. A Conditional Knockout Mouse Model Reveals a Critical Role of PKD1 in Osteoblast Differentiation and Bone Development in SCIENTIFIC REPORTS
  • 2017-09-04. Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis in NATURE GENETICS
  • 2012-06-17. Genome-wide efficient mixed-model analysis for association studies in NATURE GENETICS
  • 2015-09-14. Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture in NATURE
  • 2019-01-03. Specific functions of TET1 and TET2 in regulating mesenchymal cell lineage determination in EPIGENETICS & CHROMATIN
  • 2018-06-28. Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation in NATURE GENETICS
  • 2014-03-12. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone in NATURE
  • 2012-04-15. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture in NATURE GENETICS
  • 2013-12-13. IL-17A-mediated sRANK ligand elevation involved in postmenopausal osteoporosis in OSTEOPOROSIS INTERNATIONAL
  • 2015-02-02. Efficient Bayesian mixed-model analysis increases association power in large cohorts in NATURE GENETICS
  • 2017-08-09. Implicating candidate genes at GWAS signals by leveraging topologically associating domains in EUROPEAN JOURNAL OF HUMAN GENETICS
  • 2018-12-31. An atlas of genetic influences on osteoporosis in humans and mice in NATURE GENETICS
  • 2016-02-12. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? in CELL DEATH & DIFFERENTIATION
  • 2009-11-03. Osteoimmunology and the effects of the immune system on bone in NATURE REVIEWS RHEUMATOLOGY
  • 2018-10-26. Organizational principles of 3D genome architecture in NATURE REVIEWS GENETICS
  • 2001-09. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis in BIOGERONTOLOGY
  • 2019-03-19. Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density in NATURE COMMUNICATIONS
  • 2008-02-10. Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome) in NATURE GENETICS
  • 2016-02-08. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations in OSTEOPOROSIS INTERNATIONAL
  • 1996-10. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I α 1 gene in NATURE GENETICS
  • 2010-06-20. Common SNPs explain a large proportion of the heritability for human height in NATURE GENETICS
  • 2009-06-19. IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling in CELL DEATH & DIFFERENTIATION
  • 2008-06-11. Osteoclast size is controlled by Fra-2 through LIF/LIF-receptor signalling and hypoxia in NATURE
  • 2015-09-28. An atlas of genetic correlations across human diseases and traits in NATURE GENETICS
  • 2014-06-02. De novo SOX11 mutations cause Coffin–Siris syndrome in NATURE COMMUNICATIONS
  • 2000-09. Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease in NATURE GENETICS
  • 2016-08-26. TGFβ-induced switch from adipogenic to osteogenic differentiation of human mesenchymal stem cells: identification of drug targets for prevention of fat cell differentiation in STEM CELL RESEARCH & THERAPY
  • Journal

    TITLE

    Genome Biology

    ISSUE

    1

    VOLUME

    22

    Author Affiliations

  • Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
  • Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
  • MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
  • Imaging Platform, Broad Institute of MIT and Harvard, 02140, Cambridge, MA, USA
  • Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
  • Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH, USA
  • Department of Medicine and College of Nursing, Creighton University School of Medicine, Omaha, NB, USA
  • Division of Pulmonary Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
  • Center for Endocrinology, Diabetes & Metabolism, Children’s Hospital Los Angeles, Los Angeles, CA, USA
  • Department of Epidemiology and Population Science, University of Hawaii Cancer Center, Honolulu, HI, USA
  • Division of Pediatric Endocrinology, Columbia University Medical Center, New York, NY, USA
  • Childhood Cancer Data Lab, Alex’s Lemonade Stand Foundation, Philadelphia, PA, USA
  • Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
  • Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13059-020-02207-9

    DOI

    http://dx.doi.org/10.1186/s13059-020-02207-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1134304494

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33397451


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Genetics", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adolescent", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Bone Density", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Bone Development", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Bone Diseases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Bone and Bones", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Child", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Child, Preschool", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Chromatin", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Chromosome Mapping", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cross-Sectional Studies", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Editing", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genetic Predisposition to Disease", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genome-Wide Association Study", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genomics", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Nuclear Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Osteoblasts", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Osteogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Phenotype", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Polymorphism, Single Nucleotide", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Promoter Regions, Genetic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Quantitative Trait Loci", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA-Binding Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Young Adult", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA", 
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cousminer", 
            "givenName": "Diana L.", 
            "id": "sg:person.01241713161.69", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01241713161.69"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wagley", 
            "givenName": "Yadav", 
            "id": "sg:person.01223441550.28", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223441550.28"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pippin", 
            "givenName": "James A.", 
            "id": "sg:person.015755767310.62", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015755767310.62"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK", 
              "id": "http://www.grid.ac/institutes/grid.5337.2", 
              "name": [
                "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Elhakeem", 
            "givenName": "Ahmed", 
            "id": "sg:person.0733614044.75", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0733614044.75"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Imaging Platform, Broad Institute of MIT and Harvard, 02140, Cambridge, MA, USA", 
              "id": "http://www.grid.ac/institutes/grid.66859.34", 
              "name": [
                "Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA", 
                "Imaging Platform, Broad Institute of MIT and Harvard, 02140, Cambridge, MA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Way", 
            "givenName": "Gregory P.", 
            "id": "sg:person.012232050721.28", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012232050721.28"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pahl", 
            "givenName": "Matthew C.", 
            "id": "sg:person.011273432453.17", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011273432453.17"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "McCormack", 
            "givenName": "Shana E.", 
            "id": "sg:person.0621137767.66", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0621137767.66"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Chesi", 
            "givenName": "Alessandra", 
            "id": "sg:person.01000567777.88", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01000567777.88"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Gastroenterology, Hepatology and Nutrition, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA", 
                "Division of Gastroenterology, Hepatology and Nutrition, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mitchell", 
            "givenName": "Jonathan A.", 
            "id": "sg:person.01177154406.58", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177154406.58"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Gastroenterology, Hepatology and Nutrition, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Division of Gastroenterology, Hepatology and Nutrition, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kindler", 
            "givenName": "Joseph M.", 
            "id": "sg:person.0646630531.02", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0646630531.02"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK", 
              "id": "http://www.grid.ac/institutes/grid.5337.2", 
              "name": [
                "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Baird", 
            "givenName": "Denis", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK", 
              "id": "http://www.grid.ac/institutes/grid.5337.2", 
              "name": [
                "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hartley", 
            "givenName": "April", 
            "id": "sg:person.0624210431.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0624210431.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK", 
              "id": "http://www.grid.ac/institutes/grid.5337.2", 
              "name": [
                "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Howe", 
            "givenName": "Laura", 
            "id": "sg:person.01214543021.64", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214543021.64"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pediatrics, Cincinnati Children\u2019s Hospital, University of Cincinnati, Cincinnati, OH, USA", 
              "id": "http://www.grid.ac/institutes/grid.239573.9", 
              "name": [
                "Department of Pediatrics, Cincinnati Children\u2019s Hospital, University of Cincinnati, Cincinnati, OH, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kalkwarf", 
            "givenName": "Heidi J.", 
            "id": "sg:person.012246615407.88", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012246615407.88"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Medicine and College of Nursing, Creighton University School of Medicine, Omaha, NB, USA", 
              "id": "http://www.grid.ac/institutes/grid.254748.8", 
              "name": [
                "Department of Medicine and College of Nursing, Creighton University School of Medicine, Omaha, NB, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lappe", 
            "givenName": "Joan M.", 
            "id": "sg:person.0714345342.23", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0714345342.23"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lu", 
            "givenName": "Sumei", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Leonard", 
            "givenName": "Michelle E.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Johnson", 
            "givenName": "Matthew E.", 
            "id": "sg:person.07451256347.32", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07451256347.32"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Pulmonary Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239552.a", 
              "name": [
                "Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
                "Division of Pulmonary Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hakonarson", 
            "givenName": "Hakon", 
            "id": "sg:person.010700526417.77", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010700526417.77"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Endocrinology, Diabetes & Metabolism, Children\u2019s Hospital Los Angeles, Los Angeles, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239546.f", 
              "name": [
                "Center for Endocrinology, Diabetes & Metabolism, Children\u2019s Hospital Los Angeles, Los Angeles, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gilsanz", 
            "givenName": "Vicente", 
            "id": "sg:person.01372421417.05", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01372421417.05"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Epidemiology and Population Science, University of Hawaii Cancer Center, Honolulu, HI, USA", 
              "id": "http://www.grid.ac/institutes/grid.410445.0", 
              "name": [
                "Department of Epidemiology and Population Science, University of Hawaii Cancer Center, Honolulu, HI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Shepherd", 
            "givenName": "John A.", 
            "id": "sg:person.01054355272.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054355272.00"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Pediatric Endocrinology, Columbia University Medical Center, New York, NY, USA", 
              "id": "http://www.grid.ac/institutes/grid.239585.0", 
              "name": [
                "Division of Pediatric Endocrinology, Columbia University Medical Center, New York, NY, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Oberfield", 
            "givenName": "Sharon E.", 
            "id": "sg:person.01234712127.03", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01234712127.03"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Childhood Cancer Data Lab, Alex\u2019s Lemonade Stand Foundation, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.430722.0", 
              "name": [
                "Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA", 
                "Childhood Cancer Data Lab, Alex\u2019s Lemonade Stand Foundation, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Greene", 
            "givenName": "Casey S.", 
            "id": "sg:person.01322375346.84", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01322375346.84"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kelly", 
            "givenName": "Andrea", 
            "id": "sg:person.0614120513.76", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0614120513.76"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK", 
              "id": "http://www.grid.ac/institutes/grid.5337.2", 
              "name": [
                "MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lawlor", 
            "givenName": "Deborah A.", 
            "id": "sg:person.012720665624.27", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012720665624.27"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA", 
                "Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA", 
                "Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Voight", 
            "givenName": "Benjamin F.", 
            "id": "sg:person.0653212145.73", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653212145.73"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wells", 
            "givenName": "Andrew D.", 
            "id": "sg:person.0612153065.21", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0612153065.21"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
                "Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zemel", 
            "givenName": "Babette S.", 
            "id": "sg:person.0773506111.36", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0773506111.36"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hankenson", 
            "givenName": "Kurt D.", 
            "id": "sg:person.01100224732.81", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01100224732.81"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA", 
              "id": "http://www.grid.ac/institutes/grid.25879.31", 
              "name": [
                "Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA", 
                "Center for Spatial and Functional Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA", 
                "Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Grant", 
            "givenName": "Struan F. A.", 
            "id": "sg:person.010130357332.96", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010130357332.96"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/35046102", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033250938", 
              "https://doi.org/10.1038/35046102"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41467-019-09302-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1112851731", 
              "https://doi.org/10.1038/s41467-019-09302-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/79128", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045186509", 
              "https://doi.org/10.1038/79128"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep40505", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001188851", 
              "https://doi.org/10.1038/srep40505"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2310", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046029840", 
              "https://doi.org/10.1038/ng.2310"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1023/a:1011513223894", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018871641", 
              "https://doi.org/10.1023/a:1011513223894"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41588-018-0302-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1110718663", 
              "https://doi.org/10.1038/s41588-018-0302-x"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00198-013-2548-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036804728", 
              "https://doi.org/10.1007/s00198-013-2548-6"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature13146", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018681803", 
              "https://doi.org/10.1038/nature13146"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cdd.2009.74", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051254042", 
              "https://doi.org/10.1038/cdd.2009.74"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2007.66", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009855400", 
              "https://doi.org/10.1038/ng.2007.66"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.3949", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091429840", 
              "https://doi.org/10.1038/ng.3949"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms11840", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006369067", 
              "https://doi.org/10.1038/ncomms11840"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cdd.2015.168", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033921991", 
              "https://doi.org/10.1038/cdd.2015.168"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.3190", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041665159", 
              "https://doi.org/10.1038/ng.3190"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41588-018-0154-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1105156420", 
              "https://doi.org/10.1038/s41588-018-0154-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature14878", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039034540", 
              "https://doi.org/10.1038/nature14878"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2249", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052981137", 
              "https://doi.org/10.1038/ng.2249"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41576-018-0060-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1107841303", 
              "https://doi.org/10.1038/s41576-018-0060-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.608", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015057090", 
              "https://doi.org/10.1038/ng.608"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00198-015-3440-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011118641", 
              "https://doi.org/10.1007/s00198-015-3440-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ejhg.2017.108", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1091101897", 
              "https://doi.org/10.1038/ejhg.2017.108"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13072-018-0247-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1111064114", 
              "https://doi.org/10.1186/s13072-018-0247-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.3406", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016405801", 
              "https://doi.org/10.1038/ng.3406"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms5011", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048014942", 
              "https://doi.org/10.1038/ncomms5011"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature07019", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036153578", 
              "https://doi.org/10.1038/nature07019"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrrheum.2009.217", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028525793", 
              "https://doi.org/10.1038/nrrheum.2009.217"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng1096-203", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042845000", 
              "https://doi.org/10.1038/ng1096-203"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s13287-016-0375-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048737783", 
              "https://doi.org/10.1186/s13287-016-0375-3"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2021-01-04", 
        "datePublishedReg": "2021-01-04", 
        "description": "BackgroundBone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype by modeling longitudinal bone accrual across 11,000 bone scans in a cohort of healthy children and adolescents, followed by genome-wide association studies (GWAS) and variant-to-gene mapping with functional follow-up.ResultsWe identify 40 loci, 35 not previously reported, with various degrees of supportive evidence, half residing in topological associated domains harboring known bone genes. Of several loci potentially associated with later-life fracture risk, a candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3). Variant-to-gene mapping combining ATAC-seq to assay open chromatin with high-resolution promoter-focused Capture C identifies contacts between GWAS loci and nearby gene promoters. siRNA knockdown of gene expression supports the putative effector gene at three specific loci in two osteoblast cell models. Finally, using CRISPR-Cas9 genome editing, we confirm that the immediate genomic region harboring the putative causal SNP influences PRPF38A expression, a location which is predicted to coincide with a set of binding sites for relevant transcription factors.ConclusionsUsing a new longitudinal approach, we expand the number of genetic loci putatively associated with pediatric bone gain. Functional follow-up in appropriate cell models finds novel candidate genes impacting bone accrual. Our data also raise the possibility that the cell fate decision between osteogenic and adipogenic lineages is important in normal bone accrual.", 
        "genre": "article", 
        "id": "sg:pub.10.1186/s13059-020-02207-9", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.8470208", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.10029284", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2527905", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.4241495", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.7613815", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.8555341", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.9330254", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2705204", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.8631539", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1023439", 
            "issn": [
              "1474-760X", 
              "1465-6906"
            ], 
            "name": "Genome Biology", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "22"
          }
        ], 
        "keywords": [
          "genome-wide association studies", 
          "effector genes", 
          "gene mapping", 
          "association studies", 
          "nearby gene promoters", 
          "putative effector genes", 
          "candidate effector genes", 
          "cell fate decisions", 
          "relevant transcription factors", 
          "novel candidate genes", 
          "appropriate cell models", 
          "osteoblast cell model", 
          "open chromatin", 
          "GWAS loci", 
          "fate decisions", 
          "ATAC-seq", 
          "genomic regions", 
          "genome editing", 
          "transcription factors", 
          "novel loci", 
          "cell model", 
          "specific loci", 
          "gene promoter", 
          "genetic loci", 
          "bone genes", 
          "candidate genes", 
          "gene expression", 
          "adipogenic lineages", 
          "genetic discoveries", 
          "siRNA knockdown", 
          "genes", 
          "loci", 
          "lifelong skeletal health", 
          "dynamic phenotypes", 
          "longitudinal bones", 
          "expression", 
          "compelling evidence", 
          "chromatin", 
          "lineages", 
          "CRISPR", 
          "promoter", 
          "knockdown", 
          "variants", 
          "phenotype", 
          "editing", 
          "bone accrual", 
          "mapping", 
          "discovery", 
          "domain", 
          "sites", 
          "evidence", 
          "region", 
          "pediatric bone", 
          "supportive evidence", 
          "skeletal health", 
          "study", 
          "bone", 
          "factors", 
          "BackgroundBone", 
          "number", 
          "ResultsWe", 
          "location", 
          "contact", 
          "data", 
          "possibility", 
          "set", 
          "model", 
          "health", 
          "degree", 
          "gain", 
          "approach", 
          "accruals", 
          "risk", 
          "cohort", 
          "study design", 
          "design", 
          "decisions", 
          "fracture risk", 
          "scans", 
          "longitudinal approach", 
          "uncertainty", 
          "cross-sectional study design", 
          "bone scan", 
          "healthy children", 
          "bone gain", 
          "lookup", 
          "children", 
          "adolescents"
        ], 
        "name": "Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual", 
        "pagination": "1", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1134304494"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1186/s13059-020-02207-9"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "33397451"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1186/s13059-020-02207-9", 
          "https://app.dimensions.ai/details/publication/pub.1134304494"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-11-24T21:05", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221124/entities/gbq_results/article/article_887.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1186/s13059-020-02207-9"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s13059-020-02207-9'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s13059-020-02207-9'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s13059-020-02207-9'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s13059-020-02207-9'


     

    This table displays all metadata directly associated to this object as RDF triples.

    642 TRIPLES      21 PREDICATES      169 URIs      132 LITERALS      34 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1186/s13059-020-02207-9 schema:about N074a338eea1d4b72b3282afc866e700c
    2 N0c80370655304ea09b995690143106df
    3 N1641be4f525646b2aebdb15014fae56a
    4 N1a640152768d4b23afd2d936a7c652a8
    5 N1c5bd2d6752645228f493eda575fc2fd
    6 N1e991fca9b5642caa226dd9459b05b9c
    7 N2f683a2608174631b72199568c93631b
    8 N2fd4ad2b4a604b21bf7d4afa144fe054
    9 N3357cdae811540509d83cd5fd491f935
    10 N33c4154440e24f92805f41e6df1d29e9
    11 N3517fea260da409ca8df334f89cb48b3
    12 N3e8c3525f971463e92cf3527e7881570
    13 N53566b07559e43109d6ca68b13e4c344
    14 N61cef19d977d464f9df7d116853ede1b
    15 N64e0e0fc47fa4ac9abc3b7095408b98b
    16 N70ef2200fc7449eca8a7867b12254be7
    17 N898880cfda6d46ce88dd06a0d3194df2
    18 N907b1fa3e356440581ab6179408819ca
    19 Na359fd81d6824bd087ca5bcede9332bd
    20 Na6425e4de65d4e548bc6bdc92a6cc290
    21 Na7b21e2ad09b4ae9b7b25e9655a93746
    22 Nafccbb1fec284ad2bbf150629e4caed2
    23 Nb7b669659aab43389ec3b88576103720
    24 Nbbfbdcc6771547d48794b6ff5a0af119
    25 Nbf7e11f0272c47c9aaf19ccd258b9d03
    26 Nc4af5b3a3fcf4a99bfd2a8df2fcee8bb
    27 Nf0be59efa55c41a0b1378cecd8360479
    28 anzsrc-for:06
    29 anzsrc-for:0604
    30 schema:author Nc6d1e5319a244d78a3a784418e6d07bb
    31 schema:citation sg:pub.10.1007/s00198-013-2548-6
    32 sg:pub.10.1007/s00198-015-3440-3
    33 sg:pub.10.1023/a:1011513223894
    34 sg:pub.10.1038/35046102
    35 sg:pub.10.1038/79128
    36 sg:pub.10.1038/cdd.2009.74
    37 sg:pub.10.1038/cdd.2015.168
    38 sg:pub.10.1038/ejhg.2017.108
    39 sg:pub.10.1038/nature07019
    40 sg:pub.10.1038/nature13146
    41 sg:pub.10.1038/nature14878
    42 sg:pub.10.1038/ncomms11840
    43 sg:pub.10.1038/ncomms5011
    44 sg:pub.10.1038/ng.2007.66
    45 sg:pub.10.1038/ng.2249
    46 sg:pub.10.1038/ng.2310
    47 sg:pub.10.1038/ng.3190
    48 sg:pub.10.1038/ng.3406
    49 sg:pub.10.1038/ng.3949
    50 sg:pub.10.1038/ng.608
    51 sg:pub.10.1038/ng1096-203
    52 sg:pub.10.1038/nrrheum.2009.217
    53 sg:pub.10.1038/s41467-019-09302-x
    54 sg:pub.10.1038/s41576-018-0060-8
    55 sg:pub.10.1038/s41588-018-0154-4
    56 sg:pub.10.1038/s41588-018-0302-x
    57 sg:pub.10.1038/srep40505
    58 sg:pub.10.1186/s13072-018-0247-4
    59 sg:pub.10.1186/s13287-016-0375-3
    60 schema:datePublished 2021-01-04
    61 schema:datePublishedReg 2021-01-04
    62 schema:description BackgroundBone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype by modeling longitudinal bone accrual across 11,000 bone scans in a cohort of healthy children and adolescents, followed by genome-wide association studies (GWAS) and variant-to-gene mapping with functional follow-up.ResultsWe identify 40 loci, 35 not previously reported, with various degrees of supportive evidence, half residing in topological associated domains harboring known bone genes. Of several loci potentially associated with later-life fracture risk, a candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3). Variant-to-gene mapping combining ATAC-seq to assay open chromatin with high-resolution promoter-focused Capture C identifies contacts between GWAS loci and nearby gene promoters. siRNA knockdown of gene expression supports the putative effector gene at three specific loci in two osteoblast cell models. Finally, using CRISPR-Cas9 genome editing, we confirm that the immediate genomic region harboring the putative causal SNP influences PRPF38A expression, a location which is predicted to coincide with a set of binding sites for relevant transcription factors.ConclusionsUsing a new longitudinal approach, we expand the number of genetic loci putatively associated with pediatric bone gain. Functional follow-up in appropriate cell models finds novel candidate genes impacting bone accrual. Our data also raise the possibility that the cell fate decision between osteogenic and adipogenic lineages is important in normal bone accrual.
    63 schema:genre article
    64 schema:isAccessibleForFree true
    65 schema:isPartOf N0e0f0a65167c4c6882b67bd962e251e1
    66 Nd7db91a073424b7291c51ac6cb48a2ea
    67 sg:journal.1023439
    68 schema:keywords ATAC-seq
    69 BackgroundBone
    70 CRISPR
    71 GWAS loci
    72 ResultsWe
    73 accruals
    74 adipogenic lineages
    75 adolescents
    76 approach
    77 appropriate cell models
    78 association studies
    79 bone
    80 bone accrual
    81 bone gain
    82 bone genes
    83 bone scan
    84 candidate effector genes
    85 candidate genes
    86 cell fate decisions
    87 cell model
    88 children
    89 chromatin
    90 cohort
    91 compelling evidence
    92 contact
    93 cross-sectional study design
    94 data
    95 decisions
    96 degree
    97 design
    98 discovery
    99 domain
    100 dynamic phenotypes
    101 editing
    102 effector genes
    103 evidence
    104 expression
    105 factors
    106 fate decisions
    107 fracture risk
    108 gain
    109 gene expression
    110 gene mapping
    111 gene promoter
    112 genes
    113 genetic discoveries
    114 genetic loci
    115 genome editing
    116 genome-wide association studies
    117 genomic regions
    118 health
    119 healthy children
    120 knockdown
    121 lifelong skeletal health
    122 lineages
    123 location
    124 loci
    125 longitudinal approach
    126 longitudinal bones
    127 lookup
    128 mapping
    129 model
    130 nearby gene promoters
    131 novel candidate genes
    132 novel loci
    133 number
    134 open chromatin
    135 osteoblast cell model
    136 pediatric bone
    137 phenotype
    138 possibility
    139 promoter
    140 putative effector genes
    141 region
    142 relevant transcription factors
    143 risk
    144 scans
    145 set
    146 siRNA knockdown
    147 sites
    148 skeletal health
    149 specific loci
    150 study
    151 study design
    152 supportive evidence
    153 transcription factors
    154 uncertainty
    155 variants
    156 schema:name Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual
    157 schema:pagination 1
    158 schema:productId N54399240c4fa4fb78831fb7e93a09a63
    159 N8166b2c372f748fc8911143ed6b390b4
    160 Nfd2489353cad4db5bb5c2f4940f77076
    161 schema:sameAs https://app.dimensions.ai/details/publication/pub.1134304494
    162 https://doi.org/10.1186/s13059-020-02207-9
    163 schema:sdDatePublished 2022-11-24T21:05
    164 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    165 schema:sdPublisher N12b0dfae0e184cf589b1a08d415cd34d
    166 schema:url https://doi.org/10.1186/s13059-020-02207-9
    167 sgo:license sg:explorer/license/
    168 sgo:sdDataset articles
    169 rdf:type schema:ScholarlyArticle
    170 N025db79c46e84fc385da898fec08d83b schema:affiliation grid-institutes:grid.239552.a
    171 schema:familyName Lu
    172 schema:givenName Sumei
    173 rdf:type schema:Person
    174 N048a807e093b4ed8aeae123b769512f3 rdf:first N56576afda71f45e79837345a09d56470
    175 rdf:rest N1e0a9a8dae584ea0a61e76901caeaa02
    176 N074a338eea1d4b72b3282afc866e700c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    177 schema:name Gene Editing
    178 rdf:type schema:DefinedTerm
    179 N0c80370655304ea09b995690143106df schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    180 schema:name Male
    181 rdf:type schema:DefinedTerm
    182 N0e0f0a65167c4c6882b67bd962e251e1 schema:issueNumber 1
    183 rdf:type schema:PublicationIssue
    184 N0f411245af394d52b979db7bfc7d2b21 rdf:first sg:person.011273432453.17
    185 rdf:rest Ne11c611f76204c1a942deb398d754c1f
    186 N12b0dfae0e184cf589b1a08d415cd34d schema:name Springer Nature - SN SciGraph project
    187 rdf:type schema:Organization
    188 N1641be4f525646b2aebdb15014fae56a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    189 schema:name Osteogenesis
    190 rdf:type schema:DefinedTerm
    191 N1a640152768d4b23afd2d936a7c652a8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    192 schema:name Adolescent
    193 rdf:type schema:DefinedTerm
    194 N1c5bd2d6752645228f493eda575fc2fd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    195 schema:name Young Adult
    196 rdf:type schema:DefinedTerm
    197 N1cdd514b0ae2484a87802f752cf4d17a rdf:first sg:person.0733614044.75
    198 rdf:rest N37d10b9e3d9f49cb8211d53b818d6f9b
    199 N1e0a9a8dae584ea0a61e76901caeaa02 rdf:first sg:person.07451256347.32
    200 rdf:rest N5938ea0761e34137ad49447c29f3a149
    201 N1e991fca9b5642caa226dd9459b05b9c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    202 schema:name Child
    203 rdf:type schema:DefinedTerm
    204 N2f683a2608174631b72199568c93631b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    205 schema:name Bone Density
    206 rdf:type schema:DefinedTerm
    207 N2fd4ad2b4a604b21bf7d4afa144fe054 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    208 schema:name Bone Diseases
    209 rdf:type schema:DefinedTerm
    210 N3357cdae811540509d83cd5fd491f935 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    211 schema:name RNA-Binding Proteins
    212 rdf:type schema:DefinedTerm
    213 N33c4154440e24f92805f41e6df1d29e9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    214 schema:name Genomics
    215 rdf:type schema:DefinedTerm
    216 N3517fea260da409ca8df334f89cb48b3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    217 schema:name Cross-Sectional Studies
    218 rdf:type schema:DefinedTerm
    219 N37d10b9e3d9f49cb8211d53b818d6f9b rdf:first sg:person.012232050721.28
    220 rdf:rest N0f411245af394d52b979db7bfc7d2b21
    221 N3e46d92c3eb2455aafe2fa75406601d5 rdf:first sg:person.0653212145.73
    222 rdf:rest N751cb18dbe9f47ceb34e3d38ec3fb39c
    223 N3e8c3525f971463e92cf3527e7881570 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    224 schema:name Bone and Bones
    225 rdf:type schema:DefinedTerm
    226 N4dfccbc1ff9c446d9ab8be0593097827 rdf:first sg:person.01372421417.05
    227 rdf:rest N62535536f5c44bd08ae3c734d663717f
    228 N53566b07559e43109d6ca68b13e4c344 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    229 schema:name Humans
    230 rdf:type schema:DefinedTerm
    231 N54399240c4fa4fb78831fb7e93a09a63 schema:name doi
    232 schema:value 10.1186/s13059-020-02207-9
    233 rdf:type schema:PropertyValue
    234 N56576afda71f45e79837345a09d56470 schema:affiliation grid-institutes:grid.239552.a
    235 schema:familyName Leonard
    236 schema:givenName Michelle E.
    237 rdf:type schema:Person
    238 N5938ea0761e34137ad49447c29f3a149 rdf:first sg:person.010700526417.77
    239 rdf:rest N4dfccbc1ff9c446d9ab8be0593097827
    240 N5bb5d08a02fc4d3e91260af1fb1c8220 rdf:first sg:person.01223441550.28
    241 rdf:rest Ne74896dd47ea42bf9329e1d37b9cb5c4
    242 N61cef19d977d464f9df7d116853ede1b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    243 schema:name Gene Expression
    244 rdf:type schema:DefinedTerm
    245 N622ec2a977c5460499d961d01a0ac11e rdf:first N025db79c46e84fc385da898fec08d83b
    246 rdf:rest N048a807e093b4ed8aeae123b769512f3
    247 N62535536f5c44bd08ae3c734d663717f rdf:first sg:person.01054355272.00
    248 rdf:rest Nd0f7867f976b408e88ed65766f468319
    249 N64e0e0fc47fa4ac9abc3b7095408b98b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    250 schema:name Quantitative Trait Loci
    251 rdf:type schema:DefinedTerm
    252 N696e94e130d94105a278acac5d9463cb rdf:first N8c000606f6e34a1ca27155fb5f901343
    253 rdf:rest N8545cf76dd0c4cf796057ac8b5cc9436
    254 N6e4d459a63e24ca7835cc30259eceab2 rdf:first sg:person.0773506111.36
    255 rdf:rest Na64bfd0041674d2b9ea29818b551c34c
    256 N70ef2200fc7449eca8a7867b12254be7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    257 schema:name Osteoblasts
    258 rdf:type schema:DefinedTerm
    259 N751cb18dbe9f47ceb34e3d38ec3fb39c rdf:first sg:person.0612153065.21
    260 rdf:rest N6e4d459a63e24ca7835cc30259eceab2
    261 N7b724d5576fa46ceaac371ea9fec9a1a rdf:first sg:person.0646630531.02
    262 rdf:rest N696e94e130d94105a278acac5d9463cb
    263 N8166b2c372f748fc8911143ed6b390b4 schema:name dimensions_id
    264 schema:value pub.1134304494
    265 rdf:type schema:PropertyValue
    266 N8545cf76dd0c4cf796057ac8b5cc9436 rdf:first sg:person.0624210431.34
    267 rdf:rest N8f8513e4db204bf6aa15946eb164dc2e
    268 N898880cfda6d46ce88dd06a0d3194df2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    269 schema:name Child, Preschool
    270 rdf:type schema:DefinedTerm
    271 N8c000606f6e34a1ca27155fb5f901343 schema:affiliation grid-institutes:grid.5337.2
    272 schema:familyName Baird
    273 schema:givenName Denis
    274 rdf:type schema:Person
    275 N8f8513e4db204bf6aa15946eb164dc2e rdf:first sg:person.01214543021.64
    276 rdf:rest Nbb7fd5fb189e455582d885c286419307
    277 N907b1fa3e356440581ab6179408819ca schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    278 schema:name Polymorphism, Single Nucleotide
    279 rdf:type schema:DefinedTerm
    280 N966e286eae4b4932bd109a55803f8f08 rdf:first sg:person.010130357332.96
    281 rdf:rest rdf:nil
    282 N9a9a3f56ac364f8c8dd4cbf3d841a2c6 rdf:first sg:person.0714345342.23
    283 rdf:rest N622ec2a977c5460499d961d01a0ac11e
    284 Na359fd81d6824bd087ca5bcede9332bd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    285 schema:name Promoter Regions, Genetic
    286 rdf:type schema:DefinedTerm
    287 Na6425e4de65d4e548bc6bdc92a6cc290 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    288 schema:name Genetic Predisposition to Disease
    289 rdf:type schema:DefinedTerm
    290 Na64bfd0041674d2b9ea29818b551c34c rdf:first sg:person.01100224732.81
    291 rdf:rest N966e286eae4b4932bd109a55803f8f08
    292 Na7b21e2ad09b4ae9b7b25e9655a93746 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    293 schema:name Nuclear Proteins
    294 rdf:type schema:DefinedTerm
    295 Nab460e78002d46e997c0a9bf8a757501 rdf:first sg:person.01177154406.58
    296 rdf:rest N7b724d5576fa46ceaac371ea9fec9a1a
    297 Nafccbb1fec284ad2bbf150629e4caed2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    298 schema:name Bone Development
    299 rdf:type schema:DefinedTerm
    300 Nb7b669659aab43389ec3b88576103720 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    301 schema:name Chromatin
    302 rdf:type schema:DefinedTerm
    303 Nb7b6d0f1a3cc447bbc6a28f4b0f1796f rdf:first sg:person.012720665624.27
    304 rdf:rest N3e46d92c3eb2455aafe2fa75406601d5
    305 Nbb7fd5fb189e455582d885c286419307 rdf:first sg:person.012246615407.88
    306 rdf:rest N9a9a3f56ac364f8c8dd4cbf3d841a2c6
    307 Nbbfbdcc6771547d48794b6ff5a0af119 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    308 schema:name Female
    309 rdf:type schema:DefinedTerm
    310 Nbf7e11f0272c47c9aaf19ccd258b9d03 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    311 schema:name Genome-Wide Association Study
    312 rdf:type schema:DefinedTerm
    313 Nc4af5b3a3fcf4a99bfd2a8df2fcee8bb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    314 schema:name Phenotype
    315 rdf:type schema:DefinedTerm
    316 Nc6d1e5319a244d78a3a784418e6d07bb rdf:first sg:person.01241713161.69
    317 rdf:rest N5bb5d08a02fc4d3e91260af1fb1c8220
    318 Nd0f7867f976b408e88ed65766f468319 rdf:first sg:person.01234712127.03
    319 rdf:rest Nf6f52e3d1874410bbd9292cc20c1b8c3
    320 Nd7db91a073424b7291c51ac6cb48a2ea schema:volumeNumber 22
    321 rdf:type schema:PublicationVolume
    322 Ne11c611f76204c1a942deb398d754c1f rdf:first sg:person.0621137767.66
    323 rdf:rest Ne5ad81ddb5c2462184ee74596f304d01
    324 Ne5ad81ddb5c2462184ee74596f304d01 rdf:first sg:person.01000567777.88
    325 rdf:rest Nab460e78002d46e997c0a9bf8a757501
    326 Ne6be1bba78624893b4677b1c51628c8e rdf:first sg:person.0614120513.76
    327 rdf:rest Nb7b6d0f1a3cc447bbc6a28f4b0f1796f
    328 Ne74896dd47ea42bf9329e1d37b9cb5c4 rdf:first sg:person.015755767310.62
    329 rdf:rest N1cdd514b0ae2484a87802f752cf4d17a
    330 Nf0be59efa55c41a0b1378cecd8360479 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    331 schema:name Chromosome Mapping
    332 rdf:type schema:DefinedTerm
    333 Nf6f52e3d1874410bbd9292cc20c1b8c3 rdf:first sg:person.01322375346.84
    334 rdf:rest Ne6be1bba78624893b4677b1c51628c8e
    335 Nfd2489353cad4db5bb5c2f4940f77076 schema:name pubmed_id
    336 schema:value 33397451
    337 rdf:type schema:PropertyValue
    338 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    339 schema:name Biological Sciences
    340 rdf:type schema:DefinedTerm
    341 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    342 schema:name Genetics
    343 rdf:type schema:DefinedTerm
    344 sg:grant.10029284 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    345 rdf:type schema:MonetaryGrant
    346 sg:grant.2527905 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    347 rdf:type schema:MonetaryGrant
    348 sg:grant.2705204 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    349 rdf:type schema:MonetaryGrant
    350 sg:grant.4241495 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    351 rdf:type schema:MonetaryGrant
    352 sg:grant.7613815 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    353 rdf:type schema:MonetaryGrant
    354 sg:grant.8470208 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    355 rdf:type schema:MonetaryGrant
    356 sg:grant.8555341 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    357 rdf:type schema:MonetaryGrant
    358 sg:grant.8631539 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    359 rdf:type schema:MonetaryGrant
    360 sg:grant.9330254 http://pending.schema.org/fundedItem sg:pub.10.1186/s13059-020-02207-9
    361 rdf:type schema:MonetaryGrant
    362 sg:journal.1023439 schema:issn 1465-6906
    363 1474-760X
    364 schema:name Genome Biology
    365 schema:publisher Springer Nature
    366 rdf:type schema:Periodical
    367 sg:person.01000567777.88 schema:affiliation grid-institutes:grid.239552.a
    368 schema:familyName Chesi
    369 schema:givenName Alessandra
    370 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01000567777.88
    371 rdf:type schema:Person
    372 sg:person.010130357332.96 schema:affiliation grid-institutes:grid.25879.31
    373 schema:familyName Grant
    374 schema:givenName Struan F. A.
    375 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010130357332.96
    376 rdf:type schema:Person
    377 sg:person.01054355272.00 schema:affiliation grid-institutes:grid.410445.0
    378 schema:familyName Shepherd
    379 schema:givenName John A.
    380 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01054355272.00
    381 rdf:type schema:Person
    382 sg:person.010700526417.77 schema:affiliation grid-institutes:grid.239552.a
    383 schema:familyName Hakonarson
    384 schema:givenName Hakon
    385 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010700526417.77
    386 rdf:type schema:Person
    387 sg:person.01100224732.81 schema:affiliation grid-institutes:grid.214458.e
    388 schema:familyName Hankenson
    389 schema:givenName Kurt D.
    390 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01100224732.81
    391 rdf:type schema:Person
    392 sg:person.011273432453.17 schema:affiliation grid-institutes:grid.239552.a
    393 schema:familyName Pahl
    394 schema:givenName Matthew C.
    395 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011273432453.17
    396 rdf:type schema:Person
    397 sg:person.01177154406.58 schema:affiliation grid-institutes:grid.239552.a
    398 schema:familyName Mitchell
    399 schema:givenName Jonathan A.
    400 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177154406.58
    401 rdf:type schema:Person
    402 sg:person.01214543021.64 schema:affiliation grid-institutes:grid.5337.2
    403 schema:familyName Howe
    404 schema:givenName Laura
    405 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214543021.64
    406 rdf:type schema:Person
    407 sg:person.012232050721.28 schema:affiliation grid-institutes:grid.66859.34
    408 schema:familyName Way
    409 schema:givenName Gregory P.
    410 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012232050721.28
    411 rdf:type schema:Person
    412 sg:person.01223441550.28 schema:affiliation grid-institutes:grid.214458.e
    413 schema:familyName Wagley
    414 schema:givenName Yadav
    415 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223441550.28
    416 rdf:type schema:Person
    417 sg:person.012246615407.88 schema:affiliation grid-institutes:grid.239573.9
    418 schema:familyName Kalkwarf
    419 schema:givenName Heidi J.
    420 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012246615407.88
    421 rdf:type schema:Person
    422 sg:person.01234712127.03 schema:affiliation grid-institutes:grid.239585.0
    423 schema:familyName Oberfield
    424 schema:givenName Sharon E.
    425 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01234712127.03
    426 rdf:type schema:Person
    427 sg:person.01241713161.69 schema:affiliation grid-institutes:grid.239552.a
    428 schema:familyName Cousminer
    429 schema:givenName Diana L.
    430 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01241713161.69
    431 rdf:type schema:Person
    432 sg:person.012720665624.27 schema:affiliation grid-institutes:grid.5337.2
    433 schema:familyName Lawlor
    434 schema:givenName Deborah A.
    435 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012720665624.27
    436 rdf:type schema:Person
    437 sg:person.01322375346.84 schema:affiliation grid-institutes:grid.430722.0
    438 schema:familyName Greene
    439 schema:givenName Casey S.
    440 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01322375346.84
    441 rdf:type schema:Person
    442 sg:person.01372421417.05 schema:affiliation grid-institutes:grid.239546.f
    443 schema:familyName Gilsanz
    444 schema:givenName Vicente
    445 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01372421417.05
    446 rdf:type schema:Person
    447 sg:person.015755767310.62 schema:affiliation grid-institutes:grid.239552.a
    448 schema:familyName Pippin
    449 schema:givenName James A.
    450 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015755767310.62
    451 rdf:type schema:Person
    452 sg:person.0612153065.21 schema:affiliation grid-institutes:grid.25879.31
    453 schema:familyName Wells
    454 schema:givenName Andrew D.
    455 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0612153065.21
    456 rdf:type schema:Person
    457 sg:person.0614120513.76 schema:affiliation grid-institutes:grid.25879.31
    458 schema:familyName Kelly
    459 schema:givenName Andrea
    460 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0614120513.76
    461 rdf:type schema:Person
    462 sg:person.0621137767.66 schema:affiliation grid-institutes:grid.25879.31
    463 schema:familyName McCormack
    464 schema:givenName Shana E.
    465 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0621137767.66
    466 rdf:type schema:Person
    467 sg:person.0624210431.34 schema:affiliation grid-institutes:grid.5337.2
    468 schema:familyName Hartley
    469 schema:givenName April
    470 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0624210431.34
    471 rdf:type schema:Person
    472 sg:person.0646630531.02 schema:affiliation grid-institutes:grid.239552.a
    473 schema:familyName Kindler
    474 schema:givenName Joseph M.
    475 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0646630531.02
    476 rdf:type schema:Person
    477 sg:person.0653212145.73 schema:affiliation grid-institutes:grid.25879.31
    478 schema:familyName Voight
    479 schema:givenName Benjamin F.
    480 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653212145.73
    481 rdf:type schema:Person
    482 sg:person.0714345342.23 schema:affiliation grid-institutes:grid.254748.8
    483 schema:familyName Lappe
    484 schema:givenName Joan M.
    485 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0714345342.23
    486 rdf:type schema:Person
    487 sg:person.0733614044.75 schema:affiliation grid-institutes:grid.5337.2
    488 schema:familyName Elhakeem
    489 schema:givenName Ahmed
    490 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0733614044.75
    491 rdf:type schema:Person
    492 sg:person.07451256347.32 schema:affiliation grid-institutes:grid.239552.a
    493 schema:familyName Johnson
    494 schema:givenName Matthew E.
    495 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07451256347.32
    496 rdf:type schema:Person
    497 sg:person.0773506111.36 schema:affiliation grid-institutes:grid.25879.31
    498 schema:familyName Zemel
    499 schema:givenName Babette S.
    500 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0773506111.36
    501 rdf:type schema:Person
    502 sg:pub.10.1007/s00198-013-2548-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036804728
    503 https://doi.org/10.1007/s00198-013-2548-6
    504 rdf:type schema:CreativeWork
    505 sg:pub.10.1007/s00198-015-3440-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011118641
    506 https://doi.org/10.1007/s00198-015-3440-3
    507 rdf:type schema:CreativeWork
    508 sg:pub.10.1023/a:1011513223894 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018871641
    509 https://doi.org/10.1023/a:1011513223894
    510 rdf:type schema:CreativeWork
    511 sg:pub.10.1038/35046102 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033250938
    512 https://doi.org/10.1038/35046102
    513 rdf:type schema:CreativeWork
    514 sg:pub.10.1038/79128 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045186509
    515 https://doi.org/10.1038/79128
    516 rdf:type schema:CreativeWork
    517 sg:pub.10.1038/cdd.2009.74 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051254042
    518 https://doi.org/10.1038/cdd.2009.74
    519 rdf:type schema:CreativeWork
    520 sg:pub.10.1038/cdd.2015.168 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033921991
    521 https://doi.org/10.1038/cdd.2015.168
    522 rdf:type schema:CreativeWork
    523 sg:pub.10.1038/ejhg.2017.108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091101897
    524 https://doi.org/10.1038/ejhg.2017.108
    525 rdf:type schema:CreativeWork
    526 sg:pub.10.1038/nature07019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036153578
    527 https://doi.org/10.1038/nature07019
    528 rdf:type schema:CreativeWork
    529 sg:pub.10.1038/nature13146 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018681803
    530 https://doi.org/10.1038/nature13146
    531 rdf:type schema:CreativeWork
    532 sg:pub.10.1038/nature14878 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039034540
    533 https://doi.org/10.1038/nature14878
    534 rdf:type schema:CreativeWork
    535 sg:pub.10.1038/ncomms11840 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006369067
    536 https://doi.org/10.1038/ncomms11840
    537 rdf:type schema:CreativeWork
    538 sg:pub.10.1038/ncomms5011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048014942
    539 https://doi.org/10.1038/ncomms5011
    540 rdf:type schema:CreativeWork
    541 sg:pub.10.1038/ng.2007.66 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009855400
    542 https://doi.org/10.1038/ng.2007.66
    543 rdf:type schema:CreativeWork
    544 sg:pub.10.1038/ng.2249 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052981137
    545 https://doi.org/10.1038/ng.2249
    546 rdf:type schema:CreativeWork
    547 sg:pub.10.1038/ng.2310 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046029840
    548 https://doi.org/10.1038/ng.2310
    549 rdf:type schema:CreativeWork
    550 sg:pub.10.1038/ng.3190 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041665159
    551 https://doi.org/10.1038/ng.3190
    552 rdf:type schema:CreativeWork
    553 sg:pub.10.1038/ng.3406 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016405801
    554 https://doi.org/10.1038/ng.3406
    555 rdf:type schema:CreativeWork
    556 sg:pub.10.1038/ng.3949 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091429840
    557 https://doi.org/10.1038/ng.3949
    558 rdf:type schema:CreativeWork
    559 sg:pub.10.1038/ng.608 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015057090
    560 https://doi.org/10.1038/ng.608
    561 rdf:type schema:CreativeWork
    562 sg:pub.10.1038/ng1096-203 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042845000
    563 https://doi.org/10.1038/ng1096-203
    564 rdf:type schema:CreativeWork
    565 sg:pub.10.1038/nrrheum.2009.217 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028525793
    566 https://doi.org/10.1038/nrrheum.2009.217
    567 rdf:type schema:CreativeWork
    568 sg:pub.10.1038/s41467-019-09302-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1112851731
    569 https://doi.org/10.1038/s41467-019-09302-x
    570 rdf:type schema:CreativeWork
    571 sg:pub.10.1038/s41576-018-0060-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107841303
    572 https://doi.org/10.1038/s41576-018-0060-8
    573 rdf:type schema:CreativeWork
    574 sg:pub.10.1038/s41588-018-0154-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105156420
    575 https://doi.org/10.1038/s41588-018-0154-4
    576 rdf:type schema:CreativeWork
    577 sg:pub.10.1038/s41588-018-0302-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1110718663
    578 https://doi.org/10.1038/s41588-018-0302-x
    579 rdf:type schema:CreativeWork
    580 sg:pub.10.1038/srep40505 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001188851
    581 https://doi.org/10.1038/srep40505
    582 rdf:type schema:CreativeWork
    583 sg:pub.10.1186/s13072-018-0247-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111064114
    584 https://doi.org/10.1186/s13072-018-0247-4
    585 rdf:type schema:CreativeWork
    586 sg:pub.10.1186/s13287-016-0375-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048737783
    587 https://doi.org/10.1186/s13287-016-0375-3
    588 rdf:type schema:CreativeWork
    589 grid-institutes:grid.214458.e schema:alternateName Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
    590 schema:name Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
    591 rdf:type schema:Organization
    592 grid-institutes:grid.239546.f schema:alternateName Center for Endocrinology, Diabetes & Metabolism, Children’s Hospital Los Angeles, Los Angeles, CA, USA
    593 schema:name Center for Endocrinology, Diabetes & Metabolism, Children’s Hospital Los Angeles, Los Angeles, CA, USA
    594 rdf:type schema:Organization
    595 grid-institutes:grid.239552.a schema:alternateName Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    596 Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    597 Division of Pulmonary Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    598 schema:name Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    599 Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA
    600 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    601 Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
    602 Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    603 Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    604 Division of Pulmonary Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    605 rdf:type schema:Organization
    606 grid-institutes:grid.239573.9 schema:alternateName Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH, USA
    607 schema:name Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH, USA
    608 rdf:type schema:Organization
    609 grid-institutes:grid.239585.0 schema:alternateName Division of Pediatric Endocrinology, Columbia University Medical Center, New York, NY, USA
    610 schema:name Division of Pediatric Endocrinology, Columbia University Medical Center, New York, NY, USA
    611 rdf:type schema:Organization
    612 grid-institutes:grid.254748.8 schema:alternateName Department of Medicine and College of Nursing, Creighton University School of Medicine, Omaha, NB, USA
    613 schema:name Department of Medicine and College of Nursing, Creighton University School of Medicine, Omaha, NB, USA
    614 rdf:type schema:Organization
    615 grid-institutes:grid.25879.31 schema:alternateName Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
    616 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    617 Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
    618 Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    619 schema:name Center for Spatial and Functional Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    620 Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA
    621 Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
    622 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    623 Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
    624 Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    625 Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    626 Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
    627 Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    628 rdf:type schema:Organization
    629 grid-institutes:grid.410445.0 schema:alternateName Department of Epidemiology and Population Science, University of Hawaii Cancer Center, Honolulu, HI, USA
    630 schema:name Department of Epidemiology and Population Science, University of Hawaii Cancer Center, Honolulu, HI, USA
    631 rdf:type schema:Organization
    632 grid-institutes:grid.430722.0 schema:alternateName Childhood Cancer Data Lab, Alex’s Lemonade Stand Foundation, Philadelphia, PA, USA
    633 schema:name Childhood Cancer Data Lab, Alex’s Lemonade Stand Foundation, Philadelphia, PA, USA
    634 Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA
    635 rdf:type schema:Organization
    636 grid-institutes:grid.5337.2 schema:alternateName MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
    637 schema:name MRC Integrative Epidemiology Unit, Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
    638 rdf:type schema:Organization
    639 grid-institutes:grid.66859.34 schema:alternateName Imaging Platform, Broad Institute of MIT and Harvard, 02140, Cambridge, MA, USA
    640 schema:name Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA, USA
    641 Imaging Platform, Broad Institute of MIT and Harvard, 02140, Cambridge, MA, USA
    642 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...