Defining the role of common variation in the genomic and biological architecture of adult human height

Andrew R. Wood, Tonu Esko, Jian Yang, Sailaja Vedantam, Tune H. Pers, Stefan Gustafsson, Audrey Y. Chu, Karol Estrada, Jian'an Luan, Zoltán Kutalik, Najaf Amin, Martin L. Buchkovich, Damien C. Croteau-Chonka, Felix R. Day, Yanan Duan, Tove Fall, Rudolf Fehrmann, Teresa Ferreira, Anne U. Jackson, Juha KarjalainenKen Sin Lo, Adam E. Locke, Reedik Mägi, Evelin Mihailov, Eleonora Porcu, Joshua C. Randall, André Scherag, Anna A. E. Vinkhuyzen, Harm-Jan Westra, Thomas W. Winkler, Tsegaselassie Workalemahu, Jing Hua Zhao, Devin Absher, Eva Albrecht, Denise Anderson, Jeffrey Baron, Marian Beekman, Ayse Demirkan, Georg B. Ehret, Bjarke Feenstra, Mary F. Feitosa, Krista Fischer, Ross M. Fraser, Anuj Goel, Jian Gong, Anne E. Justice, Stavroula Kanoni, Alex S. F. Doney, Andrew D. Morris, Colin N. A. Palmer, Electronic Medical Records and Genomics (eEMERGE) Consortium, MIGen Consortium, PAGE Consortium, LifeLines Cohort Study

    Research output: Contribution to journalArticlepeer-review

    1318 Citations (Scopus)


    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

    Original languageEnglish
    Pages (from-to)1173-1186
    Number of pages14
    JournalNature Genetics
    Issue number11
    Publication statusPublished - Nov 2014


    • Adult
    • Analysis of variance
    • Body height
    • European Continental Ancestry Group
    • Genetic variation
    • Genetics, Population
    • Genome-wide association Study
    • Humans
    • Oligonucleotide Array Sequence Analysis
    • Polymorphism, Single nucleotide


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