Article abstract


Nature Genetics 40, 575 - 583 (2008)
Published online: 6 April 2008 | doi:10.1038/ng.121

Genome-wide association analysis identifies 20 loci that influence adult height

Michael N Weedon1,2,23, Hana Lango1,2,23, Cecilia M Lindgren3,4, Chris Wallace5, David M Evans6, Massimo Mangino7, Rachel M Freathy1,2, John R B Perry1,2, Suzanne Stevens7, Alistair S Hall8, Nilesh J Samani7, Beverly Shields2, Inga Prokopenko3,4, Martin Farrall9, Anna Dominiczak10, Diabetes Genetics Initiative21, The Wellcome Trust Case Control Consortium21, Toby Johnson11,12,13, Sven Bergmann11,12, Jacques S Beckmann11,14, Peter Vollenweider15, Dawn M Waterworth16, Vincent Mooser16, Colin N A Palmer17, Andrew D Morris18, Willem H Ouwehand19,20, Cambridge GEM Consortium22, Mark Caulfield5, Patricia B Munroe5, Andrew T Hattersley1,2, Mark I McCarthy3,4 & Timothy M Frayling1,2


Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 times 10- 7, with 10 reaching P < 1 times 10- 10). Combined, the 20 SNPs explain approx3% of height variation, with a approx5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.

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  1. Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK.
  2. Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK.
  3. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
  4. Oxford Centre for Diabetes, Endocrinology and Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
  5. Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine, Charterhouse Square, London EC1M 6BQ, UK.
  6. Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol BS8 2PR, UK.
  7. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.
  8. Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.
  9. Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
  10. British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
  11. Department of Medical Genetics, University of Lausanne, Lausanne 1011, Switzerland.
  12. Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
  13. Institut Universitaire de Médecine Sociale et Préventive, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.
  14. Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.
  15. Department of Medicine, Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.
  16. Medical Genetics/Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA.
  17. Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
  18. Diabetes Research Group, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
  19. Department of Haematology, University of Cambridge, Long Road, Cambridge CB2 2BT, UK.
  20. National Health Service Blood and Transplant, Cambridge Centre, Long Road, Cambridge CB2 2BT, UK.
  21. A full list of authors is provided in the Supplementary Note online.
  22. A full list of authors and affiliations appears at the end of this paper.
  23. These authors contributed equally to this work.
  24. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  25. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  26. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, UK.

Correspondence to: Timothy M Frayling1,2 e-mail: Tim.Frayling@pms.ac.uk



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