Identification of ten loci associated with height highlights new biological pathways in human growth View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-04-06

AUTHORS

Guillaume Lettre, Anne U Jackson, Christian Gieger, Fredrick R Schumacher, Sonja I Berndt, Serena Sanna, Susana Eyheramendy, Benjamin F Voight, Johannah L Butler, Candace Guiducci, Thomas Illig, Rachel Hackett, Iris M Heid, Kevin B Jacobs, Valeriya Lyssenko, Manuela Uda, Michael Boehnke, Stephen J Chanock, Leif C Groop, Frank B Hu, Bo Isomaa, Peter Kraft, Leena Peltonen, Veikko Salomaa, David Schlessinger, David J Hunter, Richard B Hayes, Gonçalo R Abecasis, H-Erich Wichmann, Karen L Mohlke, Joel N Hirschhorn

ABSTRACT

Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 × 10−7 to 8 × 10−22). Together, these 12 loci account for ∼2% of the population variation in height. Individuals with ≤8 height-increasing alleles and ≥16 height-increasing alleles differ in height by ∼3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. More... »

PAGES

584-591

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    5

    VOLUME

    40

    Author Affiliations

  • Divisions of Genetics and Endocrinology and Program in Genomics, Children's Hospital, 02115, Boston, Massachusetts, USA
  • Department of Biostatistics, Center for Statistical Genetics, University of Michigan, 48109, Ann Arbor, Michigan, USA
  • Department of Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, University of Munich, 81377, Munich, Germany
  • Department of Epidemiology, Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  • Division of Cancer Epidemiology and Genetics, Department of Health and Human Services (DHHS), Occupational and Environmental Epidemiology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), 20892, Bethesda, Maryland, USA
  • Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, 09042, Monserrato, Cagliari, Italy
  • Center for Human Genetic Research, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 02142, Cambridge, Massachusetts, USA
  • Institute of Epidemiology, GSF National Research Center for Environment and Health, 85764, Neuherberg, Germany
  • Bioinformed Consulting Services, 20877, Gaithersburg, Maryland, USA
  • Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, 205 02, Malmö, Sweden
  • Division of Cancer Epidemiology and Genetics, Laboratory of Translational Genomics, NCI, NIH, DHHS, 20892, Bethesda, Maryland, USA
  • Department of Medicine, Helsinki University Central Hospital, and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland
  • Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
  • Folkhälsan Research Center, Helsinki, Finland
  • Department of Molecular Medicine, National Public Health Institute and Department of Medical Genetics, University of Helsinki, FI-00014, Helsinki, Finland
  • Department of Epidemiology and Health Promotion. National Public Health Institute, FI-00300, Helsinki, Finland
  • Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, 21224, Baltimore, Maryland, USA
  • Department of Genetics, University of North Carolina, 27599, Chapel Hill, North Carolina, USA
  • Department of Genetics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.125

    DOI

    http://dx.doi.org/10.1038/ng.125

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1023249798

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18391950


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