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

Wood, A.R.; Esko, T.; Yang, J.; Vedantam, S.; Pers, T.H.; Gustafsson, S.; Chu, A.Y.; Estrada, K.; Luan, J.; Kutalik, Z.; Amin, N.; Buchkovich, M.L.; Croteau Chonka, D.C.; Day, F.R.; Duan, Y.; Fall, T.; Fehrmann, R.; Ferreira, T.; Jackson, A.U.; Karjalainen, J.; K. S., L.; Locke, A.E.; Mägi, R.; Mihailov, E.; Porcu, E.; Randall, J.C.; Scherag, A.; Vinkhuyzen, A.A.E.; Westra, H.; Winkler, T.W.; Workalemahu, T.; Zhao, J.H.; Absher, D.; Albrecht, E.; Anderson, D.; Baron, J.; Beekman, M.; Demirkan, A.; Ehret, G.B.; Feenstra, B.; Feitosa, M.F.; Fischer, K.; Fraser, R.M.; Goel, A.; Gong, J.; Justice, A.E.; Kanoni, S.; Kleber, M.E.; Kristiansson, K.; Lim, U.; Lotay, V.; Lui, J.C.; Mangino, M.; Leach, I.M.; Medina Gomez, C.; Nalls, M.A.; Nyholt, D.R.; Palmer, C.D.; Pasko, D.; Pechlivanis, S.; Prokopenko, I.; Ried, J.S.; Ripke, S.; Shungin, D.; Stancáková, A.; Strawbridge, R.J.; Sung, Y.J.; Tanaka, T.; Teumer, A.; Trompet, S.; van der Laan, S.W.; van Setten, J.; Van Vliet Ostaptchouk, J.V.; Wang, Z.; Yengo, L.; Zhang, W.; Afzal, U.; Arnlöv, J.; Arscott, G.M.; Bandinelli, S.; Barrett, A.; Bellis, C.; Bennett, A.J.; Berne, C.; Blüher, M.; Bolton, J.L.; Böttcher, Y.; Boyd, H.A.; Bruinenberg, M.; Buckley, B.M.; Buyske, S.; Caspersen, I.H.; Chines, P.S.; Clarke, R.; Claudi Boehm, S.; Cooper, M.; Daw, E.W.; De Jong, P.A.; Deelen, J.; Delgado, G.; Denny, J.C.; Dhonukshe Rutten, R.; Dimitriou, M.; Doney, A.S.F.; Dörr, M.; Eklund, N.; Eury, E.; Folkersen, L.; Garcia, M.E.; Geller, F.; Giedraitis, V.; A. S., G.; Grallert, H.; Grammer, T.B.; Gräßler, J.; Grönberg, H.; de Groot, L.C.P.G.M.; Groves, C.J.; Haessler, J.; Hall, P.; Haller, T.; Hallmans, G.; Hannemann, A.; Hartman, C.A.; Hassinen, M.; Hayward, C.; Heard Costa, N.L.; Helmer, Q.; Hemani, G.; Henders, A.K.; Hillege, H.L.; Hlatky, M.A.; Hoffmann, W.; Hoffmann, P.; Holmen, O.; Houwing Duistermaat, J.J.; Illig, T.; Isaacs, A.; James, A.L.; Jeff, J.; Johansen, B.; Johansson, A.; Jolley, J.; Juliusdottir, T.; Junttila, J.; Kho, A.N.; Kinnunen, L.; Klopp, N.; Kocher, T.; Kratzer, W.; Lichtner, P.; Lind, L.; Lindström, J.; Lobbens, S.; Lorentzon, M.; Lu, Y.; Lyssenko, V.; Magnusson, P.K.E.; Mahajan, A.; Maillard, M.; Mcardle, W.L.; Mckenzie, C.A.; Mclachlan, S.; Mclaren, P.J.; Menni, C.; Merger, S.; Milani, L.; Moayyeri, A.; Monda, K.L.; Morken, M.A.; Müller, G.; Müller Nurasyid, M.; Musk, A.W.; Narisu, N.; Nauck, M.; Nolte, I.M.; Nöthen, M.M.; Oozageer, L.; Pilz, S.; Rayner, N.W.; Renstrom, F.; Robertson, N.R.; Rose, L.M.; Roussel, R.; Sanna, S.; Scharnagl, H.; Scholtens, S.; Schumacher, F.R.; Schunkert, H.; Scott, R.A.; Sehmi, J.; Seufferlein, T.; Shi, J.; Silventoinen, K.; Smit, J.H.; Smith, A.V.; Smolonska, J.; Stanton, A.V.; Stirrups, K.; Stott, D.J.; Stringham, H.M.; Sundström, J.; Swertz, M.A.; Syvänen, A.; Tayo, B.O.; Thorleifsson, G.; Tyrer, J.P.; van Dijk, S.; van Schoor, N.M.; van der Velde, N.; van Heemst, D.; van Oort, F.V.A.; Vermeulen, S.H.; Verweij, N.; Vonk, J.M.; Waite, L.L.; Waldenberger, M.; Wennauer, R.; Wilkens, L.R.; Willenborg, C.; Wilsgaard, T.; Wojczynski, M.K.; Wong, A.; Wright, A.F.; Zhang, Q.; Arveiler, D.; Bakker, S.J.L.; Beilby, J.; Bergman, R.N.; Bergmann, S.; Biffar, R.; Blangero, J.; Boomsma, D.I.; Bornstein, S.R.; Bovet, P.; Brambilla, P.; Brown, M.J.; Campbell, H.; Caulfield, M.J.; Chakravarti, A.; Collins, R.; Collins, F.S.; Crawford, D.C.; Cupples, L.A.; Danesh, J.; de Faire, U.; den Ruijter, H.M.; Erbel, R.; Erdmann, J.; Eriksson, J.G.; Farrall, M.; Ferrannini, E.; Ferrières, J.; Ford, I.; Forouhi, N.G.; Forrester, T.; Gansevoort, R.T.; Gejman, P.V.; Gieger, C.; Golay, A.; Gottesman, O.; Gudnason, V.; Gyllensten, U.; Haas, D.W.; Hall, A.S.; Harris, T.B.; Hattersley, A.T.; Heath, A.C.; Hengstenberg, C.; Hicks, A.A.; Hindorff, L.A.; Hingorani, A.D.; Hofman, A.; Hovingh, G.K.; Humphries, S.E.; Hunt, S.C.; Hypponen, E.; Jacobs, K.B.; Jarvelin, M.; Jousilahti, P.; Jula, A.M.; Kaprio, J.; Kastelein, J.J.P.; Kayser, M.; Kee, F.; Keinanen Kiukaanniemi, S.M.; Kiemeney, L.A.; Kooner, J.S.; Kooperberg, C.; Koskinen, S.; Kovacs, P.; Kraja, A.T.; Kumari, M.; Kuusisto, J.; Lakka, T.A.; Langenberg, C.; Le Marchand, L.; Lehtimäki, T.; Lupoli, S.; Madden, P.A.F.; Männistö, S.; Manunta, P.; Marette, A.; Matise, T.C.; Mcknight, B.; Meitinger, T.; Moll, F.L.; Montgomery, G.W.; Morris, A.D.; Morris, A.P.; Murray, J.C.; Nelis, M.; Ohlsson, C.; Oldehinkel, A.J.; Ong, K.K.; Ouwehand, W.H.; Pasterkamp, G.; Peters, A.; Pramstaller, P.P.; Price, J.F.; Qi, L.; Raitakari, O.T.; Rankinen, T.; Rao, D.C.; Rice, T.K.; Ritchie, M.; Rudan, I.; Salomaa, V.; Samani, N.J.; Saramies, J.; Sarzynski, M.A.; Schwarz, P.E.H.; Sebert, S.; Sever, P.; Shuldiner, A.R.; Sinisalo, J.; Steinthorsdottir, V.; Stolk, R.P.; Tardif, J.; Tönjes, A.; Tremblay, A.; Tremoli, E.; Virtamo, J.; Vohl, M.; Amouyel, P.; Asselbergs, F.W.; Assimes, T.L.; Bochud, M.; Boehm, B.O.; Boerwinkle, E.; Bottinger, E.P.; Bouchard, C.; Cauchi, S.; Chambers, J.C.; Chanock, S.J.; Cooper, R.S.; de Bakker, P.I.W.; Dedoussis, G.; Ferrucci, L.; Franks, P.W.; Froguel, P.; Groop, L.C.; Haiman, C.A.; Hamsten, A.; Hayes, M.G.; Hui, J.; Hunter, D.J.; Hveem, K.; Jukema, J.W.; Kaplan, R.C.; Kivimaki, M.; Kuh, D.; Laakso, M.; Liu, Y.; Martin, N.G.; März, W.; Melbye, M.; Moebus, S.; Munroe, P.B.; Njølstad, I.; Oostra, B.A.; Palmer, C.N.A.; Pedersen, N.L.; Perola, M.; Pérusse, L.; Peters, U.; Powell, J.E.; Power, C.; Quertermous, T.; Rauramaa, R.; Reinmaa, E.; Ridker, P.M.; Rivadeneira, F.; Rotter, J.I.; Saaristo, T.E.; Saleheen, D.; Schlessinger, D.; Slagboom, P.E.; Snieder, H.; Spector, T.D.; Strauch, K.; Stumvoll, M.; Tuomilehto, J.; Uusitupa, M.; van der Harst, P.; Völzke, H.; Walker, M.; Wareham, N.J.; Watkins, H.; Wichmann, H.; Wilson, J.F.; Zanen, P.; Deloukas, P.; Heid, I.M.; Lindgren, C.M.; Mohlke, K.L.; Speliotes, E.K.; Thorsteinsdottir, U.; Barroso, I.; Fox, C.S.; North, K.E.; Strachan, D.P.; Beckmann, J.S.; Berndt, S.I.; Boehnke, M.; Borecki, I.B.; Mccarthy, M.I.; Metspalu, A.; Stefansson, K.; Uitterlinden, A.G.; van Duijn, C.M.; Franke, L.; Willer, C.J.; Price, A.L.; Lettre, G.; Loos, R.J.F.; Weedon, M.N.; Ingelsson, E.; O'Connell, J.R.; Abecasis, G.R.; Chasman, D.I.; Goddard, M.E.; Visscher, P.M.; Hirschhorn, J.N.; Frayling, T.M.

doi:10.1038/ng.3097

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.

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. Fehrmann, T. Ferreira, A.U. Jackson, J. Karjalainen, K.S. Lo, A.E. Locke, R. Mägi, E. Mihailov, E. Porcu, J.C. Randall, A. Scherag, A.A.E. Vinkhuyzen, H. 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, V. Lotay, J.C. Lui, M. Mangino, I.M. Leach, C. Medina Gomez, M.A. Nalls, D.R. Nyholt, C.D. Palmer, D. Pasko, S. Pechlivanis, I. Prokopenko, J.S. Ried, S. Ripke, D. Shungin, A. Stancáková, R.J. Strawbridge, Y.J. Sung, T. Tanaka, A. Teumer, S. Trompet, S.W. van der Laan, J. van Setten, J.V. Van Vliet Ostaptchouk, Z. Wang, L. Yengo, W. Zhang, U. Afzal, J. Arnlöv, G.M. Arscott, S. Bandinelli, A. Barrett, C. Bellis, A.J. Bennett, C. Berne, M. Blüher, J.L. Bolton, Y. Böttcher, H.A. Boyd, M. Bruinenberg, B.M. Buckley, S. Buyske, I.H. Caspersen, P.S. Chines, R. Clarke, S. Claudi Boehm, M. Cooper, E.W. Daw, P.A. De Jong, J. Deelen, G. Delgado, J.C. Denny, R. Dhonukshe Rutten, M. Dimitriou, A.S.F. Doney, M. Dörr, N. Eklund, E. Eury, L. Folkersen, M.E. Garcia, F. Geller, V. Giedraitis, A.S. Go, H. Grallert, T.B. Grammer, J. Gräßler, H. Grönberg, L.C.P.G.M. de Groot, C.J. Groves, J. Haessler, P. Hall, T. Haller, G. Hallmans, A. Hannemann, C.A. Hartman, M. Hassinen, C. Hayward, N.L. Heard Costa, Q. Helmer, G. Hemani, A.K. Henders, H.L. Hillege, M.A. Hlatky, W. Hoffmann, P. Hoffmann, O. Holmen, J.J. Houwing Duistermaat, T. Illig, A. Isaacs, A.L. James, J. Jeff, B. Johansen, A. Johansson, J. Jolley, T. Juliusdottir, J. Junttila, A.N. Kho, L. Kinnunen, N. Klopp, T. Kocher, W. Kratzer, P. Lichtner, L. Lind, J. Lindström, S. Lobbens, M. Lorentzon, Y. Lu, V. Lyssenko, P.K.E. Magnusson, A. Mahajan, M. Maillard, W.L. Mcardle, C.A. Mckenzie, S. Mclachlan, P.J. Mclaren, C. Menni, S. Merger, L. Milani, A. Moayyeri, K.L. Monda, M.A. Morken, G. Müller, M. Müller Nurasyid, A.W. Musk, N. Narisu, M. Nauck, I.M. Nolte, M.M. Nöthen, L. Oozageer, S. Pilz, N.W. Rayner, F. Renstrom, N.R. Robertson, L.M. Rose, R. Roussel, S. Sanna, H. Scharnagl, S. Scholtens, F.R. Schumacher, H. Schunkert, R.A. Scott, J. Sehmi, T. Seufferlein, J. Shi, K. Silventoinen, J.H. Smit, A.V. Smith, J. Smolonska, A.V. Stanton, K. Stirrups, D.J. Stott, H.M. Stringham, J. Sundström, M.A. Swertz, A. Syvänen, B.O. Tayo, G. Thorleifsson, J.P. Tyrer, S. van Dijk, N.M. van Schoor, N. van der Velde, D. van Heemst, F.V.A. van Oort, S.H. Vermeulen, N. Verweij, J.M. Vonk, L.L. Waite, M. Waldenberger, R. Wennauer, L.R. Wilkens, C. Willenborg, T. Wilsgaard, M.K. Wojczynski, A. Wong, A.F. Wright, Q. Zhang, D. Arveiler, S.J.L. Bakker, J. Beilby, R.N. Bergman, S. Bergmann, R. Biffar, J. Blangero, D.I. Boomsma, S.R. Bornstein, P. Bovet, P. Brambilla, M.J. Brown, H. Campbell, M.J. Caulfield, A. Chakravarti, R. Collins, F.S. Collins, D.C. Crawford, L.A. Cupples, J. Danesh, U. de Faire, H.M. den Ruijter, R. Erbel, J. Erdmann, J.G. Eriksson, M. Farrall, E. Ferrannini, J. Ferrières, I. Ford, N.G. Forouhi, T. Forrester, R.T. Gansevoort, P.V. Gejman, C. Gieger, A. Golay, O. Gottesman, V. Gudnason, U. Gyllensten, D.W. Haas, A.S. Hall, T.B. Harris, A.T. Hattersley, A.C. Heath, C. Hengstenberg, A.A. Hicks, L.A. Hindorff, A.D. Hingorani, A. Hofman, G.K. Hovingh, S.E. Humphries, S.C. Hunt, E. Hypponen, K.B. Jacobs, M. Jarvelin, P. Jousilahti, A.M. Jula, J. Kaprio, J.J.P. Kastelein, M. Kayser, F. Kee, S.M. Keinanen Kiukaanniemi, L.A. Kiemeney, J.S. Kooner, C. Kooperberg, S. Koskinen, P. Kovacs, A.T. Kraja, M. Kumari, J. Kuusisto, T.A. Lakka, C. Langenberg, L. Le Marchand, T. Lehtimäki, S. Lupoli, P.A.F. Madden, S. Männistö, P. Manunta, A. Marette, T.C. Matise, B. Mcknight, T. Meitinger, F.L. Moll, G.W. Montgomery, A.D. Morris, A.P. Morris, J.C. Murray, M. Nelis, C. Ohlsson, A.J. Oldehinkel, K.K. Ong, W.H. Ouwehand, G. Pasterkamp, A. Peters, P.P. Pramstaller, J.F. Price, L. Qi, O.T. Raitakari, T. Rankinen, D.C. Rao, T.K. Rice, M. Ritchie, I. Rudan, V. Salomaa, N.J. Samani, J. Saramies, M.A. Sarzynski, P.E.H. Schwarz, S. Sebert, P. Sever, A.R. Shuldiner, J. Sinisalo, V. Steinthorsdottir, R.P. Stolk, J. Tardif, A. Tönjes, A. Tremblay, E. Tremoli, J. Virtamo, M. Vohl, P. Amouyel, F.W. Asselbergs, T.L. Assimes, M. Bochud, B.O. Boehm, E. Boerwinkle, E.P. Bottinger, C. Bouchard, S. Cauchi, J.C. Chambers, S.J. Chanock, R.S. Cooper, P.I.W. de Bakker, G. Dedoussis, L. Ferrucci, P.W. Franks, P. Froguel, L.C. Groop, C.A. Haiman, A. Hamsten, M.G. Hayes, J. Hui, D.J. Hunter, K. Hveem, J.W. Jukema, R.C. Kaplan, M. Kivimaki, D. Kuh, M. Laakso, Y. Liu, N.G. Martin, W. März, M. Melbye, S. Moebus, P.B. Munroe, I. Njølstad, B.A. Oostra, C.N.A. Palmer, N.L. Pedersen, M. Perola, L. Pérusse, U. Peters, J.E. Powell, C. Power, T. Quertermous, R. Rauramaa, E. Reinmaa, P.M. Ridker, F. Rivadeneira, J.I. Rotter, T.E. Saaristo, 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. 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, 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. - In: NATURE GENETICS. - ISSN 1061-4036. - 46:11(2014 Nov), pp. 1173-1186. [10.1038/ng.3097]

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. Fehrmann;T. Ferreira;A. U. Jackson;J. Karjalainen;K. S. Lo;A. E. Locke;R. Mägi;E. Mihailov;E. Porcu;J. C. Randall;A. Scherag;A. A. E. Vinkhuyzen;H. 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;V. Lotay;J. C. Lui;M. Mangino;I. M. Leach;C. Medina Gomez;M. A. Nalls;D. R. Nyholt;C. D. Palmer;D. Pasko;S. Pechlivanis;I. Prokopenko;J. S. Ried;S. Ripke;D. Shungin;A. Stancáková;R. J. Strawbridge;Y. J. Sung;T. Tanaka;A. Teumer;S. Trompet;S. W. van der Laan;J. van Setten;J. V. Van Vliet Ostaptchouk;Z. Wang;L. Yengo;W. Zhang;U. Afzal;J. Arnlöv;G. M. Arscott;S. Bandinelli;A. Barrett;C. Bellis;A. J. Bennett;C. Berne;M. Blüher;J. L. Bolton;Y. Böttcher;H. A. Boyd;M. Bruinenberg;B. M. Buckley;S. Buyske;I. H. Caspersen;P. S. Chines;R. Clarke;S. Claudi Boehm;M. Cooper;E. W. Daw;P. A. De Jong;J. Deelen;G. Delgado;J. C. Denny;R. Dhonukshe Rutten;M. Dimitriou;A. S. F. Doney;M. Dörr;N. Eklund;E. Eury;L. Folkersen;M. E. Garcia;F. Geller;V. Giedraitis;A. S. Go;H. Grallert;T. B. Grammer;J. Gräßler;H. Grönberg;L. C. P. G. M. de Groot;C. J. Groves;J. Haessler;P. Hall;T. Haller;G. Hallmans;A. Hannemann;C. A. Hartman;M. Hassinen;C. Hayward;N. L. Heard Costa;Q. Helmer;G. Hemani;A. K. Henders;H. L. Hillege;M. A. Hlatky;W. Hoffmann;P. Hoffmann;O. Holmen;J. J. Houwing Duistermaat;T. Illig;A. Isaacs;A. L. James;J. Jeff;B. Johansen;A. Johansson;J. Jolley;T. Juliusdottir;J. Junttila;A. N. Kho;L. Kinnunen;N. Klopp;T. Kocher;W. Kratzer;P. Lichtner;L. Lind;J. Lindström;S. Lobbens;M. Lorentzon;Y. Lu;V. Lyssenko;P. K. E. Magnusson;A. Mahajan;M. Maillard;W. L. McArdle;C. A. McKenzie;S. McLachlan;P. J. McLaren;C. Menni;S. Merger;L. Milani;A. Moayyeri;K. L. Monda;M. A. Morken;G. Müller;M. Müller Nurasyid;A. W. Musk;N. Narisu;M. Nauck;I. M. Nolte;M. M. Nöthen;L. Oozageer;S. Pilz;N. W. Rayner;F. Renstrom;N. R. Robertson;L. M. Rose;R. Roussel;S. Sanna;H. Scharnagl;S. Scholtens;F. R. Schumacher;H. Schunkert;R. A. Scott;J. Sehmi;T. Seufferlein;J. Shi;K. Silventoinen;J. H. Smit;A. V. Smith;J. Smolonska;A. V. Stanton;K. Stirrups;D. J. Stott;H. M. Stringham;J. Sundström;M. A. Swertz;A. Syvänen;B. O. Tayo;G. Thorleifsson;J. P. Tyrer;S. van Dijk;N. M. van Schoor;N. van der Velde;D. van Heemst;F. V. A. van Oort;S. H. Vermeulen;N. Verweij;J. M. Vonk;L. L. Waite;M. Waldenberger;R. Wennauer;L. R. Wilkens;C. Willenborg;T. Wilsgaard;M. K. Wojczynski;A. Wong;A. F. Wright;Q. Zhang;D. Arveiler;S. J. L. Bakker;J. Beilby;R. N. Bergman;S. Bergmann;R. Biffar;J. Blangero;D. I. Boomsma;S. R. Bornstein;P. Bovet;P. Brambilla;M. J. Brown;H. Campbell;M. J. Caulfield;A. Chakravarti;R. Collins;F. S. Collins;D. C. Crawford;L. A. Cupples;J. Danesh;U. de Faire;H. M. den Ruijter;R. Erbel;J. Erdmann;J. G. Eriksson;M. Farrall;E. Ferrannini;J. Ferrières;I. Ford;N. G. Forouhi;T. Forrester;R. T. Gansevoort;P. V. Gejman;C. Gieger;A. Golay;O. Gottesman;V. Gudnason;U. Gyllensten;D. W. Haas;A. S. Hall;T. B. Harris;A. T. Hattersley;A. C. Heath;C. Hengstenberg;A. A. Hicks;L. A. Hindorff;A. D. Hingorani;A. Hofman;G. K. Hovingh;S. E. Humphries;S. C. Hunt;E. Hypponen;K. B. Jacobs;M. Jarvelin;P. Jousilahti;A. M. Jula;J. Kaprio;J. J. P. Kastelein;M. Kayser;F. Kee;S. M. Keinanen Kiukaanniemi;L. A. Kiemeney;J. S. Kooner;C. Kooperberg;S. Koskinen;P. Kovacs;A. T. Kraja;M. Kumari;J. Kuusisto;T. A. Lakka;C. Langenberg;L. Le Marchand;T. Lehtimäki;S. Lupoli;P. A. F. Madden;S. Männistö;P. Manunta;A. Marette;T. C. Matise;B. McKnight;T. Meitinger;F. L. Moll;G. W. Montgomery;A. D. Morris;A. P. Morris;J. C. Murray;M. Nelis;C. Ohlsson;A. J. Oldehinkel;K. K. Ong;W. H. Ouwehand;G. Pasterkamp;A. Peters;P. P. Pramstaller;J. F. Price;L. Qi;O. T. 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Tuomilehto;M. Uusitupa;P. van der Harst;H. Völzke;M. Walker;N. J. Wareham;H. Watkins;H. 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;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

2014

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.

Scheda breve

Scheda completa

Scheda completa (DC)

	Parole chiave
	
			genetic-variation; complex traits; heritability; mutations; SNPS
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore BIO/14 - Farmacologia
		
	Data di pubblicazione
	
			nov-2014
		
	Rivista in ANCE
	
			NATURE GENETICS
		
	DOI
	
			https://dx.doi.org/10.1038/ng.3097
		
	Tipologia
	
			Article (author)
		
	Appare nelle tipologie:
	
			01 - Articolo su periodico

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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/241832

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