Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-08-13

AUTHORS

Wei Zhou, Jonas B. Nielsen, Lars G. Fritsche, Rounak Dey, Maiken E. Gabrielsen, Brooke N. Wolford, Jonathon LeFaive, Peter VandeHaar, Sarah A. Gagliano, Aliya Gifford, Lisa A. Bastarache, Wei-Qi Wei, Joshua C. Denny, Maoxuan Lin, Kristian Hveem, Hyun Min Kang, Goncalo R. Abecasis, Cristen J. Willer, Seunggeun Lee

ABSTRACT

In genome-wide association studies (GWAS) for thousands of phenotypes in large biobanks, most binary traits have substantially fewer cases than controls. Both of the widely used approaches, the linear mixed model and the recently proposed logistic mixed model, perform poorly; they produce large type I error rates when used to analyze unbalanced case-control phenotypes. Here we propose a scalable and accurate generalized mixed model association test that uses the saddlepoint approximation to calibrate the distribution of score test statistics. This method, SAIGE (Scalable and Accurate Implementation of GEneralized mixed model), provides accurate P values even when case-control ratios are extremely unbalanced. SAIGE uses state-of-art optimization strategies to reduce computational costs; hence, it is applicable to GWAS for thousands of phenotypes by large biobanks. Through the analysis of UK Biobank data of 408,961 samples from white British participants with European ancestry for > 1,400 binary phenotypes, we show that SAIGE can efficiently analyze large sample data, controlling for unbalanced case-control ratios and sample relatedness. More... »

PAGES

1335-1341

References to SciGraph publications

  • 2010-03-07. Mixed linear model approach adapted for genome-wide association studies in NATURE GENETICS
  • 2001-12-03. Merlin—rapid analysis of dense genetic maps using sparse gene flow trees in NATURE GENETICS
  • 2011-09-04. FaST linear mixed models for genome-wide association studies in NATURE METHODS
  • 2015-02-02. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies in NATURE GENETICS
  • 2013-12-01. Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data in NATURE BIOTECHNOLOGY
  • 2012-09-16. Rapid variance components–based method for whole-genome association analysis in NATURE GENETICS
  • 2012-06-17. Genome-wide efficient mixed-model analysis for association studies in NATURE GENETICS
  • 2010-03-07. Variance component model to account for sample structure in genome-wide association studies in NATURE GENETICS
  • 2016-08-22. A reference panel of 64,976 haplotypes for genotype imputation in NATURE GENETICS
  • 2013-09-12. A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects in HUMAN GENETICS
  • 2012-05-30. Improved linear mixed models for genome-wide association studies in NATURE METHODS
  • 2015-02-02. Efficient Bayesian mixed-model analysis increases association power in large cohorts in NATURE GENETICS
  • 2014-01-29. Advantages and pitfalls in the application of mixed-model association methods in NATURE GENETICS
  • 2016-02-15. Unravelling the human genome–phenome relationship using phenome-wide association studies in NATURE REVIEWS GENETICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0184-y

    DOI

    http://dx.doi.org/10.1038/s41588-018-0184-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106070347

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30104761


    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/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Case-Control Studies", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Computer Simulation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genome-Wide Association Study", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Linear Models", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Logistic Models", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Models, Genetic", 
            "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"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA", 
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zhou", 
            "givenName": "Wei", 
            "id": "sg:person.0706552355.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706552355.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nielsen", 
            "givenName": "Jonas B.", 
            "id": "sg:person.0765074230.63", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0765074230.63"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
                "K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway", 
                "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fritsche", 
            "givenName": "Lars G.", 
            "id": "sg:person.0736477270.05", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736477270.05"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
                "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Dey", 
            "givenName": "Rounak", 
            "id": "sg:person.015420272677.53", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015420272677.53"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway", 
              "id": "http://www.grid.ac/institutes/grid.5947.f", 
              "name": [
                "K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gabrielsen", 
            "givenName": "Maiken E.", 
            "id": "sg:person.01235162135.10", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01235162135.10"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA", 
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wolford", 
            "givenName": "Brooke N.", 
            "id": "sg:person.07551500277.15", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07551500277.15"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
                "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "LeFaive", 
            "givenName": "Jonathon", 
            "id": "sg:person.013725704650.44", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013725704650.44"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
                "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "VandeHaar", 
            "givenName": "Peter", 
            "id": "sg:person.011477326353.77", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011477326353.77"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
                "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gagliano", 
            "givenName": "Sarah A.", 
            "id": "sg:person.0663520556.79", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0663520556.79"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA", 
              "id": "http://www.grid.ac/institutes/grid.152326.1", 
              "name": [
                "Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gifford", 
            "givenName": "Aliya", 
            "id": "sg:person.01355301532.13", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01355301532.13"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA", 
              "id": "http://www.grid.ac/institutes/grid.152326.1", 
              "name": [
                "Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bastarache", 
            "givenName": "Lisa A.", 
            "id": "sg:person.01022325550.35", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01022325550.35"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA", 
              "id": "http://www.grid.ac/institutes/grid.152326.1", 
              "name": [
                "Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wei", 
            "givenName": "Wei-Qi", 
            "id": "sg:person.07457322365.25", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07457322365.25"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA", 
              "id": "http://www.grid.ac/institutes/grid.412807.8", 
              "name": [
                "Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA", 
                "Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Denny", 
            "givenName": "Joshua C.", 
            "id": "sg:person.011704424024.13", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011704424024.13"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lin", 
            "givenName": "Maoxuan", 
            "id": "sg:person.010470176057.91", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010470176057.91"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway", 
              "id": "http://www.grid.ac/institutes/grid.5947.f", 
              "name": [
                "K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway", 
                "HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hveem", 
            "givenName": "Kristian", 
            "id": "sg:person.0703577540.65", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0703577540.65"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
                "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kang", 
            "givenName": "Hyun Min", 
            "id": "sg:person.013600711637.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013600711637.19"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
                "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Abecasis", 
            "givenName": "Goncalo R.", 
            "id": "sg:person.0641525362.39", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0641525362.39"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA", 
                "Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI, USA", 
                "Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Willer", 
            "givenName": "Cristen J.", 
            "id": "sg:person.01175557647.16", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01175557647.16"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA", 
                "Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lee", 
            "givenName": "Seunggeun", 
            "id": "sg:person.013062152347.40", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013062152347.40"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1007/s00439-013-1355-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048460698", 
              "https://doi.org/10.1007/s00439-013-1355-7"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2410", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036140888", 
              "https://doi.org/10.1038/ng.2410"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.1681", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006195414", 
              "https://doi.org/10.1038/nmeth.1681"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nbt.2749", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011663155", 
              "https://doi.org/10.1038/nbt.2749"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.3643", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050700099", 
              "https://doi.org/10.1038/ng.3643"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.2037", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045203738", 
              "https://doi.org/10.1038/nmeth.2037"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.546", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017784241", 
              "https://doi.org/10.1038/ng.546"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng786", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041343500", 
              "https://doi.org/10.1038/ng786"
            ], 
            "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.10.1038/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/nrg.2015.36", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026170769", 
              "https://doi.org/10.1038/nrg.2015.36"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.3211", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044444076", 
              "https://doi.org/10.1038/ng.3211"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.548", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016055940", 
              "https://doi.org/10.1038/ng.548"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng.2876", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016276818", 
              "https://doi.org/10.1038/ng.2876"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2018-08-13", 
        "datePublishedReg": "2018-08-13", 
        "description": "In genome-wide association studies (GWAS) for thousands of phenotypes in large biobanks, most binary traits have substantially fewer cases than controls. Both of the widely used approaches, the linear mixed model and the recently proposed logistic mixed model, perform poorly; they produce large type I error rates when used to analyze unbalanced case-control phenotypes. Here we propose a scalable and accurate generalized mixed model association test that uses the saddlepoint approximation to calibrate the distribution of score test statistics. This method, SAIGE (Scalable and Accurate Implementation of GEneralized mixed model), provides accurate P values even when case-control ratios are extremely unbalanced. SAIGE uses state-of-art optimization strategies to reduce computational costs; hence, it is applicable to GWAS for thousands of phenotypes by large biobanks. Through the analysis of UK Biobank data of 408,961 samples from white British participants with European ancestry for\u2009>\u20091,400 binary phenotypes, we show that SAIGE can efficiently analyze large sample data, controlling for unbalanced case-control ratios and sample relatedness.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41588-018-0184-y", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.6617285", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.7746336", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2545622", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.4317599", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.6618186", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.5124417", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2684530", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2786773", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.9424382", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.5475446", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1103138", 
            "issn": [
              "1061-4036", 
              "1546-1718"
            ], 
            "name": "Nature Genetics", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "9", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "50"
          }
        ], 
        "keywords": [
          "thousands of phenotypes", 
          "mixed model association test", 
          "sample relatedness", 
          "unbalanced case-control ratios", 
          "score test statistic", 
          "case-control phenotypes", 
          "case-control ratio", 
          "case-control imbalance", 
          "accurate p-values", 
          "art optimization strategies", 
          "saddlepoint approximation", 
          "large Type I error rates", 
          "Type I error rates", 
          "computational cost", 
          "test statistic", 
          "I error rate", 
          "SAIGE", 
          "large-scale genetic association studies", 
          "optimization strategy", 
          "large sample data", 
          "binary phenotypes", 
          "mixed models", 
          "sample data", 
          "binary traits", 
          "logistic mixed models", 
          "large biobanks", 
          "linear mixed models", 
          "UK Biobank data", 
          "approximation", 
          "genetic association studies", 
          "model", 
          "statistics", 
          "Biobank data", 
          "error rate", 
          "genome-wide association studies", 
          "distribution", 
          "approach", 
          "thousands", 
          "state", 
          "Association Test", 
          "p-value", 
          "data", 
          "association studies", 
          "cases", 
          "ratio", 
          "control", 
          "cost", 
          "values", 
          "analysis", 
          "strategies", 
          "study", 
          "samples", 
          "rate", 
          "test", 
          "imbalance", 
          "white British participants", 
          "Biobank", 
          "relatedness", 
          "traits", 
          "ancestry", 
          "participants", 
          "phenotype", 
          "European ancestry", 
          "British participants", 
          "method"
        ], 
        "name": "Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies", 
        "pagination": "1335-1341", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1106070347"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41588-018-0184-y"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "30104761"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41588-018-0184-y", 
          "https://app.dimensions.ai/details/publication/pub.1106070347"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-11-24T21:03", 
        "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_761.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41588-018-0184-y"
      }
    ]
     

    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.10.1038/s41588-018-0184-y'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41588-018-0184-y'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41588-018-0184-y'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41588-018-0184-y'


     

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

    384 TRIPLES      21 PREDICATES      113 URIs      91 LITERALS      16 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41588-018-0184-y schema:about N01e9cca27007456880eeb5aa258d6569
    2 N1cf6af6f307e41a4b8c648bb4392cf81
    3 N5bb78fabb8ed4bb68cf97c9e349e83d3
    4 N637425082f2d42dbaee297157d80e36a
    5 N794aa753971e429798efdb38b36eb4f2
    6 N889422c2bb0b47f6b2f6a886d5d0ff90
    7 N8ef5e0504baa4fb4994408117db30cf1
    8 Ncecdfe65fef4461e9162b4fa2ca61d55
    9 Nd8cd4d496f3a4ebe8cf73af27407e942
    10 anzsrc-for:06
    11 anzsrc-for:11
    12 schema:author N02d5a2c1238f4b6f92747b6cacf10a21
    13 schema:citation sg:pub.10.1007/s00439-013-1355-7
    14 sg:pub.10.1038/nbt.2749
    15 sg:pub.10.1038/ng.2310
    16 sg:pub.10.1038/ng.2410
    17 sg:pub.10.1038/ng.2876
    18 sg:pub.10.1038/ng.3190
    19 sg:pub.10.1038/ng.3211
    20 sg:pub.10.1038/ng.3643
    21 sg:pub.10.1038/ng.546
    22 sg:pub.10.1038/ng.548
    23 sg:pub.10.1038/ng786
    24 sg:pub.10.1038/nmeth.1681
    25 sg:pub.10.1038/nmeth.2037
    26 sg:pub.10.1038/nrg.2015.36
    27 schema:datePublished 2018-08-13
    28 schema:datePublishedReg 2018-08-13
    29 schema:description In genome-wide association studies (GWAS) for thousands of phenotypes in large biobanks, most binary traits have substantially fewer cases than controls. Both of the widely used approaches, the linear mixed model and the recently proposed logistic mixed model, perform poorly; they produce large type I error rates when used to analyze unbalanced case-control phenotypes. Here we propose a scalable and accurate generalized mixed model association test that uses the saddlepoint approximation to calibrate the distribution of score test statistics. This method, SAIGE (Scalable and Accurate Implementation of GEneralized mixed model), provides accurate P values even when case-control ratios are extremely unbalanced. SAIGE uses state-of-art optimization strategies to reduce computational costs; hence, it is applicable to GWAS for thousands of phenotypes by large biobanks. Through the analysis of UK Biobank data of 408,961 samples from white British participants with European ancestry for > 1,400 binary phenotypes, we show that SAIGE can efficiently analyze large sample data, controlling for unbalanced case-control ratios and sample relatedness.
    30 schema:genre article
    31 schema:isAccessibleForFree true
    32 schema:isPartOf N9d18550f55384b17a4d109b8337688ab
    33 Ne3b27e43bd6046f8a2096e2c2962eca5
    34 sg:journal.1103138
    35 schema:keywords Association Test
    36 Biobank
    37 Biobank data
    38 British participants
    39 European ancestry
    40 I error rate
    41 SAIGE
    42 Type I error rates
    43 UK Biobank data
    44 accurate p-values
    45 analysis
    46 ancestry
    47 approach
    48 approximation
    49 art optimization strategies
    50 association studies
    51 binary phenotypes
    52 binary traits
    53 case-control imbalance
    54 case-control phenotypes
    55 case-control ratio
    56 cases
    57 computational cost
    58 control
    59 cost
    60 data
    61 distribution
    62 error rate
    63 genetic association studies
    64 genome-wide association studies
    65 imbalance
    66 large Type I error rates
    67 large biobanks
    68 large sample data
    69 large-scale genetic association studies
    70 linear mixed models
    71 logistic mixed models
    72 method
    73 mixed model association test
    74 mixed models
    75 model
    76 optimization strategy
    77 p-value
    78 participants
    79 phenotype
    80 rate
    81 ratio
    82 relatedness
    83 saddlepoint approximation
    84 sample data
    85 sample relatedness
    86 samples
    87 score test statistic
    88 state
    89 statistics
    90 strategies
    91 study
    92 test
    93 test statistic
    94 thousands
    95 thousands of phenotypes
    96 traits
    97 unbalanced case-control ratios
    98 values
    99 white British participants
    100 schema:name Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies
    101 schema:pagination 1335-1341
    102 schema:productId N21a18d17dd5b410e992ecb2af4a0d547
    103 Na26d61911cb047968c3e8476a576378a
    104 Nf55277f234d6405b8443f1360f5329e6
    105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1106070347
    106 https://doi.org/10.1038/s41588-018-0184-y
    107 schema:sdDatePublished 2022-11-24T21:03
    108 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    109 schema:sdPublisher N8aa5f6baa8fe4ed49972462f14ca0ef7
    110 schema:url https://doi.org/10.1038/s41588-018-0184-y
    111 sgo:license sg:explorer/license/
    112 sgo:sdDataset articles
    113 rdf:type schema:ScholarlyArticle
    114 N01e9cca27007456880eeb5aa258d6569 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    115 schema:name Computer Simulation
    116 rdf:type schema:DefinedTerm
    117 N02d5a2c1238f4b6f92747b6cacf10a21 rdf:first sg:person.0706552355.14
    118 rdf:rest N92d9cbab2e0c4d1984bae03dfc4e7ce4
    119 N050f2bc40dcf448995227c67cc77eed8 rdf:first sg:person.0736477270.05
    120 rdf:rest N467dbc57b32c4d299f08bdce2822ad1b
    121 N1cf6af6f307e41a4b8c648bb4392cf81 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    122 schema:name Case-Control Studies
    123 rdf:type schema:DefinedTerm
    124 N21a18d17dd5b410e992ecb2af4a0d547 schema:name doi
    125 schema:value 10.1038/s41588-018-0184-y
    126 rdf:type schema:PropertyValue
    127 N31f6e7bd6b154b53ac1cdfddc33f5788 rdf:first sg:person.01175557647.16
    128 rdf:rest Nd0d93161ad15486e9b3070f58d228378
    129 N467dbc57b32c4d299f08bdce2822ad1b rdf:first sg:person.015420272677.53
    130 rdf:rest N8371ccd8ab1042e99b61530200946f2d
    131 N4d1404ae5d3c4efabaa500198476ba37 rdf:first sg:person.0663520556.79
    132 rdf:rest N9ffdbd4239bd45f6ad8c7f8f8ce544a6
    133 N5bb78fabb8ed4bb68cf97c9e349e83d3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Logistic Models
    135 rdf:type schema:DefinedTerm
    136 N6043b5e6e81b44bdbf787a91c5e8836e rdf:first sg:person.0641525362.39
    137 rdf:rest N31f6e7bd6b154b53ac1cdfddc33f5788
    138 N62009bdadc5649528eb9fbc6a24c28d5 rdf:first sg:person.011704424024.13
    139 rdf:rest N797365f1313442148b1924fccf529a2f
    140 N637425082f2d42dbaee297157d80e36a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    141 schema:name Phenotype
    142 rdf:type schema:DefinedTerm
    143 N6e28979e5f814ce19a92fb75083b166f rdf:first sg:person.011477326353.77
    144 rdf:rest N4d1404ae5d3c4efabaa500198476ba37
    145 N794aa753971e429798efdb38b36eb4f2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name Models, Genetic
    147 rdf:type schema:DefinedTerm
    148 N797365f1313442148b1924fccf529a2f rdf:first sg:person.010470176057.91
    149 rdf:rest Nc8bb061624fd48858004629354932f98
    150 N8371ccd8ab1042e99b61530200946f2d rdf:first sg:person.01235162135.10
    151 rdf:rest N86c7cb3bcc66428c83356d7721b40327
    152 N86c7cb3bcc66428c83356d7721b40327 rdf:first sg:person.07551500277.15
    153 rdf:rest Nce9b702991684517a7edf67a1c0ebaf5
    154 N889422c2bb0b47f6b2f6a886d5d0ff90 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Genome-Wide Association Study
    156 rdf:type schema:DefinedTerm
    157 N8aa5f6baa8fe4ed49972462f14ca0ef7 schema:name Springer Nature - SN SciGraph project
    158 rdf:type schema:Organization
    159 N8ef5e0504baa4fb4994408117db30cf1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    160 schema:name Linear Models
    161 rdf:type schema:DefinedTerm
    162 N8f2047065f754029869e504fffde7da0 rdf:first sg:person.013600711637.19
    163 rdf:rest N6043b5e6e81b44bdbf787a91c5e8836e
    164 N92d9cbab2e0c4d1984bae03dfc4e7ce4 rdf:first sg:person.0765074230.63
    165 rdf:rest N050f2bc40dcf448995227c67cc77eed8
    166 N9d18550f55384b17a4d109b8337688ab schema:issueNumber 9
    167 rdf:type schema:PublicationIssue
    168 N9ffdbd4239bd45f6ad8c7f8f8ce544a6 rdf:first sg:person.01355301532.13
    169 rdf:rest Nb55c356402084fe586211e16458db715
    170 Na26d61911cb047968c3e8476a576378a schema:name pubmed_id
    171 schema:value 30104761
    172 rdf:type schema:PropertyValue
    173 Na5b7c0324e1142fcab4634a876501a68 rdf:first sg:person.07457322365.25
    174 rdf:rest N62009bdadc5649528eb9fbc6a24c28d5
    175 Nb55c356402084fe586211e16458db715 rdf:first sg:person.01022325550.35
    176 rdf:rest Na5b7c0324e1142fcab4634a876501a68
    177 Nc8bb061624fd48858004629354932f98 rdf:first sg:person.0703577540.65
    178 rdf:rest N8f2047065f754029869e504fffde7da0
    179 Nce9b702991684517a7edf67a1c0ebaf5 rdf:first sg:person.013725704650.44
    180 rdf:rest N6e28979e5f814ce19a92fb75083b166f
    181 Ncecdfe65fef4461e9162b4fa2ca61d55 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    182 schema:name Polymorphism, Single Nucleotide
    183 rdf:type schema:DefinedTerm
    184 Nd0d93161ad15486e9b3070f58d228378 rdf:first sg:person.013062152347.40
    185 rdf:rest rdf:nil
    186 Nd8cd4d496f3a4ebe8cf73af27407e942 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    187 schema:name Humans
    188 rdf:type schema:DefinedTerm
    189 Ne3b27e43bd6046f8a2096e2c2962eca5 schema:volumeNumber 50
    190 rdf:type schema:PublicationVolume
    191 Nf55277f234d6405b8443f1360f5329e6 schema:name dimensions_id
    192 schema:value pub.1106070347
    193 rdf:type schema:PropertyValue
    194 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    195 schema:name Biological Sciences
    196 rdf:type schema:DefinedTerm
    197 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    198 schema:name Medical and Health Sciences
    199 rdf:type schema:DefinedTerm
    200 sg:grant.2545622 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    201 rdf:type schema:MonetaryGrant
    202 sg:grant.2684530 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    203 rdf:type schema:MonetaryGrant
    204 sg:grant.2786773 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    205 rdf:type schema:MonetaryGrant
    206 sg:grant.4317599 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    207 rdf:type schema:MonetaryGrant
    208 sg:grant.5124417 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    209 rdf:type schema:MonetaryGrant
    210 sg:grant.5475446 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    211 rdf:type schema:MonetaryGrant
    212 sg:grant.6617285 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    213 rdf:type schema:MonetaryGrant
    214 sg:grant.6618186 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    215 rdf:type schema:MonetaryGrant
    216 sg:grant.7746336 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    217 rdf:type schema:MonetaryGrant
    218 sg:grant.9424382 http://pending.schema.org/fundedItem sg:pub.10.1038/s41588-018-0184-y
    219 rdf:type schema:MonetaryGrant
    220 sg:journal.1103138 schema:issn 1061-4036
    221 1546-1718
    222 schema:name Nature Genetics
    223 schema:publisher Springer Nature
    224 rdf:type schema:Periodical
    225 sg:person.01022325550.35 schema:affiliation grid-institutes:grid.152326.1
    226 schema:familyName Bastarache
    227 schema:givenName Lisa A.
    228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01022325550.35
    229 rdf:type schema:Person
    230 sg:person.010470176057.91 schema:affiliation grid-institutes:grid.214458.e
    231 schema:familyName Lin
    232 schema:givenName Maoxuan
    233 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010470176057.91
    234 rdf:type schema:Person
    235 sg:person.011477326353.77 schema:affiliation grid-institutes:grid.214458.e
    236 schema:familyName VandeHaar
    237 schema:givenName Peter
    238 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011477326353.77
    239 rdf:type schema:Person
    240 sg:person.011704424024.13 schema:affiliation grid-institutes:grid.412807.8
    241 schema:familyName Denny
    242 schema:givenName Joshua C.
    243 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011704424024.13
    244 rdf:type schema:Person
    245 sg:person.01175557647.16 schema:affiliation grid-institutes:grid.214458.e
    246 schema:familyName Willer
    247 schema:givenName Cristen J.
    248 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01175557647.16
    249 rdf:type schema:Person
    250 sg:person.01235162135.10 schema:affiliation grid-institutes:grid.5947.f
    251 schema:familyName Gabrielsen
    252 schema:givenName Maiken E.
    253 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01235162135.10
    254 rdf:type schema:Person
    255 sg:person.013062152347.40 schema:affiliation grid-institutes:grid.214458.e
    256 schema:familyName Lee
    257 schema:givenName Seunggeun
    258 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013062152347.40
    259 rdf:type schema:Person
    260 sg:person.01355301532.13 schema:affiliation grid-institutes:grid.152326.1
    261 schema:familyName Gifford
    262 schema:givenName Aliya
    263 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01355301532.13
    264 rdf:type schema:Person
    265 sg:person.013600711637.19 schema:affiliation grid-institutes:grid.214458.e
    266 schema:familyName Kang
    267 schema:givenName Hyun Min
    268 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013600711637.19
    269 rdf:type schema:Person
    270 sg:person.013725704650.44 schema:affiliation grid-institutes:grid.214458.e
    271 schema:familyName LeFaive
    272 schema:givenName Jonathon
    273 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013725704650.44
    274 rdf:type schema:Person
    275 sg:person.015420272677.53 schema:affiliation grid-institutes:grid.214458.e
    276 schema:familyName Dey
    277 schema:givenName Rounak
    278 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015420272677.53
    279 rdf:type schema:Person
    280 sg:person.0641525362.39 schema:affiliation grid-institutes:grid.214458.e
    281 schema:familyName Abecasis
    282 schema:givenName Goncalo R.
    283 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0641525362.39
    284 rdf:type schema:Person
    285 sg:person.0663520556.79 schema:affiliation grid-institutes:grid.214458.e
    286 schema:familyName Gagliano
    287 schema:givenName Sarah A.
    288 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0663520556.79
    289 rdf:type schema:Person
    290 sg:person.0703577540.65 schema:affiliation grid-institutes:grid.5947.f
    291 schema:familyName Hveem
    292 schema:givenName Kristian
    293 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0703577540.65
    294 rdf:type schema:Person
    295 sg:person.0706552355.14 schema:affiliation grid-institutes:grid.214458.e
    296 schema:familyName Zhou
    297 schema:givenName Wei
    298 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706552355.14
    299 rdf:type schema:Person
    300 sg:person.0736477270.05 schema:affiliation grid-institutes:grid.214458.e
    301 schema:familyName Fritsche
    302 schema:givenName Lars G.
    303 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0736477270.05
    304 rdf:type schema:Person
    305 sg:person.07457322365.25 schema:affiliation grid-institutes:grid.152326.1
    306 schema:familyName Wei
    307 schema:givenName Wei-Qi
    308 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07457322365.25
    309 rdf:type schema:Person
    310 sg:person.07551500277.15 schema:affiliation grid-institutes:grid.214458.e
    311 schema:familyName Wolford
    312 schema:givenName Brooke N.
    313 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07551500277.15
    314 rdf:type schema:Person
    315 sg:person.0765074230.63 schema:affiliation grid-institutes:grid.214458.e
    316 schema:familyName Nielsen
    317 schema:givenName Jonas B.
    318 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0765074230.63
    319 rdf:type schema:Person
    320 sg:pub.10.1007/s00439-013-1355-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048460698
    321 https://doi.org/10.1007/s00439-013-1355-7
    322 rdf:type schema:CreativeWork
    323 sg:pub.10.1038/nbt.2749 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011663155
    324 https://doi.org/10.1038/nbt.2749
    325 rdf:type schema:CreativeWork
    326 sg:pub.10.1038/ng.2310 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046029840
    327 https://doi.org/10.1038/ng.2310
    328 rdf:type schema:CreativeWork
    329 sg:pub.10.1038/ng.2410 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036140888
    330 https://doi.org/10.1038/ng.2410
    331 rdf:type schema:CreativeWork
    332 sg:pub.10.1038/ng.2876 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016276818
    333 https://doi.org/10.1038/ng.2876
    334 rdf:type schema:CreativeWork
    335 sg:pub.10.1038/ng.3190 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041665159
    336 https://doi.org/10.1038/ng.3190
    337 rdf:type schema:CreativeWork
    338 sg:pub.10.1038/ng.3211 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044444076
    339 https://doi.org/10.1038/ng.3211
    340 rdf:type schema:CreativeWork
    341 sg:pub.10.1038/ng.3643 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050700099
    342 https://doi.org/10.1038/ng.3643
    343 rdf:type schema:CreativeWork
    344 sg:pub.10.1038/ng.546 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017784241
    345 https://doi.org/10.1038/ng.546
    346 rdf:type schema:CreativeWork
    347 sg:pub.10.1038/ng.548 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016055940
    348 https://doi.org/10.1038/ng.548
    349 rdf:type schema:CreativeWork
    350 sg:pub.10.1038/ng786 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041343500
    351 https://doi.org/10.1038/ng786
    352 rdf:type schema:CreativeWork
    353 sg:pub.10.1038/nmeth.1681 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006195414
    354 https://doi.org/10.1038/nmeth.1681
    355 rdf:type schema:CreativeWork
    356 sg:pub.10.1038/nmeth.2037 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045203738
    357 https://doi.org/10.1038/nmeth.2037
    358 rdf:type schema:CreativeWork
    359 sg:pub.10.1038/nrg.2015.36 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026170769
    360 https://doi.org/10.1038/nrg.2015.36
    361 rdf:type schema:CreativeWork
    362 grid-institutes:grid.152326.1 schema:alternateName Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA
    363 schema:name Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA
    364 rdf:type schema:Organization
    365 grid-institutes:grid.214458.e schema:alternateName Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA
    366 Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
    367 Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA
    368 Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI, USA
    369 schema:name Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA
    370 Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
    371 Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA
    372 Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA
    373 Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI, USA
    374 K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
    375 rdf:type schema:Organization
    376 grid-institutes:grid.412807.8 schema:alternateName Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
    377 schema:name Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA
    378 Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
    379 rdf:type schema:Organization
    380 grid-institutes:grid.5947.f schema:alternateName HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway
    381 K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
    382 schema:name HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway
    383 K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
    384 rdf:type schema:Organization
     




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


    ...