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

AR Wood, T Esko, Jiaqi Yang, S Vedantam, TH Pers, S Gustafsson, AY Chun, Karol Estrada Gil, J Luan, Z Kutalik, Najaf Amin, ML Buchkovich, DC Croteau-Chonka, FR Day, Y Duan, T Fall, R Fehrmann, T Ferreira, AU Jackson, J KarjalainenKS Lo, AE Locke, R Magi, E Mihailov, E Porcu, JC Randall, A Scherag, AAE Vinkhuyzen, HJ Westra, TW Winkler, T Workalemahu, JH Zhao, D Absher, E Albrecht, D Anderson, J Baron, M Beekman, Ayse Demirkan, GB Ehret, B Feenstra, MF Feitosa, K (Kirsten) Fischer, RM Fraser, A Goel, J Gong, AE Justice, S Kanoni, ME Kleber, K Kristiansson, U Lim, V Lotay, JC Lui, M Mangino, IM Leach, C Medina-Gomez, MA Nalls, DR Nyholt, CD Palmer, D Pasko, S Pechlivanis, I Prokopenko, JS Ried, S Ripke, D Shungin, A Stancakova, RJ Strawbridge, YJ Sung, T Tanaka, A Teumer, S Trompet, SW van der Laan, J van Setten, JV van Vliet-Ostaptchouk, ZM Wang, L Yengo, WH Zhang, U Afzal, J Arnlov, GM Arscott, S Bandinelli, A Barrett, C Bellis, AJ Bennett, C Berne, M Bluher, JL Bolton, Y Bottcher, HA Boyd, M Bruinenberg, BM Buckley, S Buyske, IH Caspersen, PS Chines, R Clarke, S Claudi-Boehm, M Cooper, EW Daw, PA Jong, J Deelen, G Delgado, JC Denny, R Dhonukshe-Rutten, M Dimitriou, ASF Doney, M Dorr, N Eklund, E Eury, L Folkersen, ME Garcia, F Geller, V Giedraitis, AS Go, H Grallert, TB Grammer, J Grassler, H Gronberg, LCPGM (Lisette) de Groot, CJ Groves, J Haessler, P Hall, T Haller, G Hallmans, A Hannemann, CA Hartman, M Hassinen, C Hayward, NL Heard-Costa, Q Helmer, G Hemani, AK Henders, HL Hillege, MA Hlatky, W Hoffmann, P Hoffmann, O Holmen, JJ Houwing-Duistermaat, T Illig, Aaron Isaacs, AL James, J Jeff, B Johansen, A Johansson, J Jolley, T Juliusdottir, J Junttila, AN Kho, L Kinnunen, N Klopp, T Kocher, W Kratzer, P Lichtner, L Lind, J Lindstrom, S Lobbens, M Lorentzon, YC Lu, V Lyssenko, PKE Magnusson, A Mahajan, M Maillard, WL McArdle, CA McKenzie, S McLachlan, PJ McLaren, C Menni, S Merger, L Milani, A Moayyeri, KL Monda, MA Morken, G Muller, M Muller-Nurasyid, AW Musk, N Narisu, M Nauck, IM (Ilja) Nolte, MM Nothen, L Oozageer, S Pilz, NW Rayner, F Renstrom, NR Robertson, LM Rose, R Roussel, S Sanna, H Scharnagl, s Scholtens, FR Schumacher, H Schunkert, RA Scott, J Sehmi, T Seufferlein, JX Shin, K Silventoinen, JH Smit, AV Smith, J Smolonska, AV Stanton, K Stirrups, DJ Stott, HM Stringham, J Sundstrom, MA Swertz, AC Syvanen, BO Tayo, G Thorleifsson, JP Tyrer, S van Dijk, NM Schoor, Nathalie van der Velde, D van Heemst, Floor Oort, SH Vermeulen, N (Niek) Verweij, JM Vonk, LL Waite, M Waldenberger, R Wennauer, LR Wilkens, C Willenborg, T Wilsgaard, MK Wojczynski, A Wong, AF Wright, QY Zhang, D Arveiler, SJL Bakker, J Beilby, RN Bergman, S Bergmann, R Biffar, J Blangero, DI Boomsma, SR Bornstein, P Bovet, P Brambilla, MJ Brown, H Campbell, MJ Caulfield, A Chakravarti, R Collins, FS Collins, DC Crawford, LA Cupples, J Danesh, U de Faire, HM den Ruijter, R Erbel, J Erdmann, JG Eriksson, M Farrall, E Ferrannini, J Ferrieres, I Ford, NG Forouhi, T Forrester, RT Gansevoort, PV Gejman, C Gieger, A Golay, O Gottesman, V Gudnason, U Gyllensten, DW Haas, AS Hall, TB Harris, AT Hattersley, AC Heath, C Hengstenberg, AA Hicks, LA Hindorff, AD Hingorani, Bert Hofman, GK Hovingh, SE Humphries, SC Hunt, E Hypponen, KB Jacobs, MR Jarvelin, P Jousilahti, AM Jula, J Kaprio, JJP Kastelein, Manfred Kayser, F Kee, SM Keinanen-Kiukaanniemi, LA Kiemeney, JS Kooner, C Kooperberg, S Koskinen, P Kovacs, AT Kraja, M Kumari, J Kuusisto, TA Lakka, C Langenberg, L Le Marchand, T Lehtimaki, S Lupoli, PAF Madden, S Mannisto, P Manunta, A Marette, TC Matise, B McKnight, T Meitinger, FL Moll, GW Montgomery, AD Morris, AP Morris, JC Murray, M Nelis, C Ohlsson, AJ (A.) Oldehinkel, KK Ong, WH Ouwehand, G Pasterkamp, A Peters, PP Pramstaller, JF Price, L Qi, OT Raitakari, T Rankinen, DC Rao, TK Rice, M Ritchie, I Rudan, V Salomaa, NJ Samani, J Saramies, MA Sarzynski, PEH Schwarz, S Sebert, P Sever, AR Shuldiner, J Sinisalo, V Steinthorsdottir, RP (Ronald) Stolk, JC Tardif, A Tonjes, A Tremblay, E Tremoli, J Virtamo, MC Vohl, P Amouyel, FW Asselbergs, TL Assimes, M Bochud, BO Boehm, E Boerwinkle, EP Bottinger, C Bouchard, S Cauchi, JC Chambers, SJ Chanock, RS Cooper, PIW de Bakker, G Dedoussis, L Ferrucci, PW Franks, P Froguel, LC Groop, CA Haiman, A Hamsten, MG Hayes, J Hui, DJ Hunter, K Hveem, JW Jukema, RC Kaplan, M Kivimaki, D Kuh, M Laakso, YM Liu, NG Martin, W Marz, M Melbye, S Moebus, PB Munroe, I Njolstad, Ben Oostra, CNA Palmer, NL Pedersen, M Perola, L Perusse, U Peters, JE Powell, C Power, T Quertermous, R Rauramaa, E Reinmaa, PM Ridker, Fernando Rivadeneira, JI Rotter, TE Saaristo, D Saleheen, D Schlessinger, PE (Eline) Slagboom, H Snieder, TD Spector, K Strauch, M Stumvoll, J Tuomilehto, M Uusitupa, P van der Harst, H Volzke, M Walker, NJ Wareham, H Watkins, HE Wichmann, JF Wilson, P Zanen, P Deloukas, IM Heid, CM Lindgren, KL Mohlke, EK Speliotes, U Thorsteinsdottir, I Barroso, CS Fox, KE North, DP Strachan, JS Beckmann, SI Berndt, M Boehnke, IB Borecki, MI McCarthy, A Metspalu, K Stefansson, André Uitterlinden, Cornelia Duijn, L Franke, CJ Willer, AL Price, G Lettre, RJF Loos, MN Weedon, E Ingelsson, JR O'Connell, GR Abecasis, DI Chasman, ME Goddard, PM Visscher, JN Hirschhorn, TM Frayling

Research output: Contribution to journalArticleAcademicpeer-review

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 similar to 2,000, similar to 3,700 and similar to 9,500 SNPs explained similar to 21%, similar to 24% and similar to 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/beta-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 languageUndefined/Unknown
Pages (from-to)1173-1186
Number of pages14
JournalNature Genetics
Volume46
Issue number11
DOIs
Publication statusPublished - 2014

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