A common variant of HMGA2 is associated with adult and childhood height in the general population View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-09-02

AUTHORS

Michael N Weedon, Guillaume Lettre, Rachel M Freathy, Cecilia M Lindgren, Benjamin F Voight, John R B Perry, Katherine S Elliott, Rachel Hackett, Candace Guiducci, Beverley Shields, Eleftheria Zeggini, Hana Lango, Valeriya Lyssenko, Nicholas J Timpson, Noel P Burtt, Nigel W Rayner, Richa Saxena, Kristin Ardlie, Jonathan H Tobias, Andrew R Ness, Susan M Ring, Colin N A Palmer, Andrew D Morris, Leena Peltonen, Veikko Salomaa, George Davey Smith, Leif C Groop, Andrew T Hattersley, Mark I McCarthy, Joel N Hirschhorn, Timothy M Frayling

ABSTRACT

Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P = 4 × 10−8). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P = 3 × 10−11, overall P = 4 × 10−16, including the genome-wide association data). We also observed the association in children (P = 1 × 10−6, N = 6,827) and a tall/short case-control study (P = 4 × 10−6, N = 3,207). We estimate that rs1042725 explains ∼0.3% of population variation in height (∼0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height. More... »

PAGES

1245-1250

Journal

TITLE

Nature Genetics

ISSUE

10

VOLUME

39

Author Affiliations

  • Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, EX2 5DW, Exeter, UK
  • Divisions of Genetics and Endocrinology and Program in Genomics, Children's Hospital, 02115, Boston, Massachusetts, USA
  • Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, OX3 7LJ, Oxford, UK
  • Center for Human Genetic Research, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, OX3 7BN, Oxford, UK
  • Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Department of Medicine, Helsinki University Central Hospital, Folkhalsan Genetic Institute, Folkhalsan Research Center and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland
  • The MRC Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Road, BS8 2PR, Bristol, UK
  • Department of Molecular Biology, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • Clinical Science at South Bristol, University of Bristol, BS2 8AE, Bristol, UK
  • Department of Oral and Dental Science, Bristol Dental School, University of Bristol, Lower Maudlin Street, BS1 2LY, Bristol, UK
  • Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, BS8 2PR, Bristol, UK
  • Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, DD1 9SY, Dundee, UK
  • Division of Medicine and Therapeutics, Diabetes Research Group, Ninewells Hospital and Medical School, University of Dundee, DD1 9SY, Dundee, UK
  • 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
  • Department of Genetics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng2121

    DOI

    http://dx.doi.org/10.1038/ng2121

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1029381463

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17767157


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