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

A.R. Wood, T. Esko, J. Yang, S. Vedantam, T.H. Pers, S. Gustafsson, A.Y. Chu, K. Estrada, J. Luan, Z. Kutalik, N. Amin, M.L. Buchkovich, D.C. Croteau-Chonka, F.R. Day, Y. Duan, T. Fall, R.S. Fehrmann, T. Ferreira, A.U. Jackson, J. KarjalainenK.S. Lo, A.E. Locke, R. Mägi, E. Mihailov, E. Porcu, J.C. Randall, A. Scherag, A.A.E. Vinkhuyzen, H.J. Westra, T.W. Winkler, T. Workalemahu, J.H. Zhao, D. Absher, E. Albrecht, D. Anderson, J. Baron, M. Beekman, A. Demirkan, G.B. Ehret, B. Feenstra, M.F. Feitosa, K. Fischer, R.M. Fraser, A. Goel, J. Gong, A.E. Justice, S. Kanoni, M.E. Kleber, K. Kristiansson, U. Lim, Q. Helmer, D.I. Boomsma, D. Saleheen, D. Schlessinger, P.E. Slagboom, H. Snieder, T.D. Spector, K. Strauch, M. Stumvoll, J. Tuomilehto, M. Uusitupa, P. van der Harst, H. Völzke, M. Walker, N.J. Wareham, H. Watkins, H.E. Wichmann, J.F. Wilson, P. Zanen, P. Deloukas, I.M. Heid, C.M. Lindgren, K.L. Mohlke, E.K. Speliotes, U. Thorsteinsdottir, I. Barroso, C.S. Fox, K.E. North, D.P. Strachan, J.S. Beckmann, S.I. Berndt, M. Boehnke, I.B. Borecki, M.I. McCarthy, A. Metspalu, J.H. Smit, S. Pilz, N.M. van Schoor, K. Stefansson, A.G. Uitterlinden, C.M. van Duijn, L. Franke, C.J. Willer, A.L. Price, G. Lettre, R.J.F. Loos, M.N. Weedon, E. Ingelsson, J.R. O'Connell, G.R. Abecasis, D.I. Chasman, M.E. Goddard, P.M. Visscher, J.N. Hirschhorn, T.M. Frayling

Research output: Contribution to JournalArticleAcademicpeer-review


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 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% 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/I 2-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 - 2014

Cohort Studies

  • Netherlands Twin Register (NTR)


Dive into the research topics of 'Defining the role of common variation in the genomic and biological architecture of adult human height'. Together they form a unique fingerprint.

Cite this