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

Michael N. Weedon, Hana Lango, Cecilia M. Lindgren, Chris Wallace, David M. Evans, Massimo Mangino, Rachel M. Freathy, John R. B. Perry, Suzanne Stevens, Alistair S. Hall, Nilesh J. Samani, Beverly Shields, Inga Prokopenko, Martin Farrall, Anna Dominiczak, Toby Johnson, Sven Bergmann, Jacques S. Beckmann, Peter Vollenweider, Dawn M. WaterworthVincent Mooser, Colin N. A. Palmer, Andrew D. Morris, Willem H. Ouwehand, Mark Caulfield, Patricia B. Munroe, Andrew T. Hattersley, Mark I. McCarthy, Timothy M. Frayling, Wellcome Trust Case Control Consor, Cambridge GEM Consortium, Diabet Genetics Initiat

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    Abstract

    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 x 10(-7), with 10 reaching P < 1 iota x 10(-10)). Combined, the 20 SNPs explain similar to 3% of height variation, with a similar to 5 cm difference between the 6.2% of people with iota 7 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.

    Original languageEnglish
    Pages (from-to)575-583
    Number of pages9
    JournalNature Genetics
    Volume40
    Issue number5
    DOIs
    Publication statusPublished - May 2008

    Keywords

    • GENETIC ASSOCIATION
    • BODY HEIGHT
    • SUSCEPTIBILITY
    • POPULATION
    • STRATIFICATION
    • OSTEOARTHRITIS
    • HERITABILITY
    • EXPRESSION
    • STATURE
    • COHORTS

    Cite this

    Weedon, M. N., Lango, H., Lindgren, C. M., Wallace, C., Evans, D. M., Mangino, M., Freathy, R. M., Perry, J. R. B., Stevens, S., Hall, A. S., Samani, N. J., Shields, B., Prokopenko, I., Farrall, M., Dominiczak, A., Johnson, T., Bergmann, S., Beckmann, J. S., Vollenweider, P., ... Wellcome Trust Case Control Consor, Cambridge GEM Consortium, Diabet Genetics Initiat (2008). Genome-wide association analysis identifies 20 loci that influence adult height. Nature Genetics, 40(5), 575-583. https://doi.org/10.1038/ng.121