Abstract
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.
Overview publication
Title | Defining the role of common variation in the genomic and biological architecture of adult human height. |
Date | November 1st, 2014 |
Issue name | Nature genetics |
Issue number | v46.11:1173-86 |
DOI | 10.1038/ng.3097 |
PubMed | 25282103 |
Authors | |
Info | McCarty CA, Starren J, Peissig P, Berg R, Rasmussen L, Linneman J, Miller A, Choudary V, Chen L, Waudby C, Kitchner T, Reeser J, Fost N, Ritchie M, Wilke RA, Chisholm RL, Avila PC, Greenland P, Hayes M, Kho A, Kibbe WA, Lemke AA, Lowe WL, Smith ME, Wolf WA, Pacheco JA, Thompson WK, Humowiecki J, Law M, Chute C, Kullo I, Koenig B, de Andrade M, Bielinski S, Pathak J, Savova G, Wu J, Henriksen J, Ding K, Hart L, Palbicki J, Larson EB, Newton K, Ludman E, Spangler L, Hart G, Carrell D, Jarvik G, Crane P, Burke W, Fullerton SM, Trinidad SB, Carlson C, Hutchinson F, McDavid A, Roden DM, Clayton E, Haines JL, Masys DR, Churchill LR, Cornfield D, Crawford D, Darbar D, Denny JC, Malin BA, Ritchie MD, Schildcrout JS, Xu H, Ramirez AH, Basford M, Pulley J, Alizadeh B, de Boer RA, Boezen HM, Bruinenberg M, Franke L, van der Harst P, Hillege HL, van der Klauw MM, Navis G, Ormel J, Postma DS, Rosmalen JG, Slaets JP, Snieder H, Stolk RP, Wolffenbuttel BH, Wijmenga C, Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, Mannucci PM, Anand S, Engert JC, Samani NJ, Schunkert H, Erdmann J, Reilly MP, Rader DJ, Morgan T, Spertus JA, Stoll M, Girelli D, McKeown PP, Patterson CC, Siscovick DS, O'Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Kathiresan S, Meigs JB, Williams G, Nathan DM, MacRae CA, O'Donnell CJ, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight B, Kathiresan S, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Voight BF, Purcell S, Nemesh J, Korn JM, McCarroll SA, Schwartz SM, Yee J, Kathiresan S, Lucas G, Subirana I, Elosua R, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, Samani NJ, Thompson JR, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall AS, Schunkert I, Erdmann J, Linsel-Nitschke P, Lieb W, Ziegler A, König IR, Hengstenberg C, Fischer M, Stark K, Grosshennig A, Preuss M, Wichmann HE, Schreiber S, Schunkert H, Samani NJ, Erdmann J, Ouwehand W, Hengstenberg C, Deloukas P, Scholz M, Cambien F, Goodall A, Reilly MP, Li M, Chen Z, Wilensky R, Matthai W, Qasim A, Hakonarson HH, Devaney J, Burnett MS, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Knouff CW, Waterworth DM, Walker MC, Mooser V, Epstein SE, Rader DJ, Scheffold T, Berger K, Stoll M, Huge A, Girelli D, Martinelli N, Olivieri O, Corrocher R, Morgan T, Spertus JA, McKeown PP, Patterson CC, Schunkert H, Erdmann J, Linsel-Nitschke P, Lieb W, Ziegler A, König I, Hengstenberg C, Fischer M, Stark K, Grosshennig A, Preuss M, Wichmann HE, Schreiber S, Hólm H, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Engert JC, Do R, Xie C, Anand S, Kathiresan S, Ardissino D, Mannucci PM, Siscovick D, O'Donnell CJ, Samani NJ, Melander O, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Altshuler D, Matise T, Buyske S, Higashio J, Williams R, Nato A, Ambite JL, Deelman E, Manolio T, Hindorff L, North KE, Heiss G, Taylor K, Franceschini N, Avery C, Graff M, Lin D, Quibrera M, Cochran B, Kao L, Umans J, Cole S, MacCluer J, Person S, Pankow J, Gross M, Boerwinkle E, Fornage M, Durda P, Jenny N, Patsy B, Arnold A, Buzkova P, Crawford D, Haines J, Murdock D, Glenn K, Brown-Gentry K, Thornton-Wells T, Dumitrescu L, Jeff J, Bush WS, Mitchell SL, Goodloe R, Wilson S, Boston J, Malinowski J, Restrepo N, Oetjens M, Fowke J, Zheng W, Spencer K, Ritchie M, Pendergrass S, Le Marchand L, Wilkens L, Park L, Tiirikainen M, Kolonel L, Lim U, Cheng I, Wang H, Shohet R, Haiman C, Stram D, Henderson B, Monroe K, Schumacher F, Kooperberg C, Peters U, Anderson G, Carlson C, Prentice R, LaCroix A, Wu C, Carty C, Gong J, Rosse S, Young A, Haessler J, Kocarnik J, Lin Y, Jackson R, Duggan D, Kuller L |
Read | Read publication |