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

Publication

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

Journal Paper/Review - Oct 5, 2014

Jousilahti Pekka, Lakka Timo A, Langenberg Claudia, Le Marchand Loic, Lehtimäki Terho, Lupoli Sara, Madden Pamela A F, Männistö Satu, Manunta Paolo, Marette André, Matise Tara C, McKnight Barbara, Kuusisto Johanna, Kumari Meena, Kraja Aldi T, Jula Antti M, Kaprio Jaakko, Kastelein John J P, Kayser Manfred, Kee Frank, Keinanen-Kiukaanniemi Sirkka M, Kiemeney Lambertus A, Kooner Jaspal S, Kooperberg Charles, Koskinen Seppo, Kovacs Peter, Meitinger Thomas, Moll Frans L, Montgomery Grant W, Rankinen Tuomo, Rao D C, Rice Treva K, Ritchie Marylyn, Rudan Igor, Salomaa Veikko, Samani Nilesh J, Saramies Jouko, Sarzynski Mark A, Schwarz Peter E H, Sebert Sylvain, Raitakari Olli T, Qi Lu, Price Jackie F, Morris Andrew D, Morris Andrew P, Murray Jeffrey C, Nelis Mari, Ohlsson Claes, Oldehinkel Albertine J, Ong Ken K, Ouwehand Willem H, Pasterkamp Gerard, Peters Annette, Pramstaller Peter P, Sever Peter, Jarvelin Marjo-Riitta, Wright Alan F, Caulfield Mark J, Chakravarti Aravinda, Collins Rory, Collins Francis S, Crawford Dana C, Cupples L Adrienne, Danesh John, de Faire Ulf, den Ruijter Hester M, Erbel Raimund, Erdmann Jeanette, Campbell Harry, Brown Morris J, Brambilla Paolo, Zhang Qunyuan, Arveiler Dominique, Bakker Stephan J L, Beilby John, Bergman Richard N, Bergmann Sven, Biffar Reiner, Blangero John, Boomsma Dorret I, Bornstein Stefan R, Bovet Pascal, Eriksson Johan G, Farrall Martin, Ferrannini Ele, Hattersley Andrew T, Heath Andrew C, Hengstenberg Christian, Hicks Andrew A, Hindorff Lucia A, Hingorani Aroon D, Hofman Albert, Hovingh G Kees, Humphries Steve E, Hunt Steven C, Hyppönen Elina, Harris Tamara B, Hall Alistair S, Haas David W, Ferrieres Jean, Ford Ian, Forouhi Nita G, Forrester Terrence, Gansevoort Ron T, Gejman Pablo V, Gieger Christian, Golay Alain, Gottesman Omri, Gudnason Vilmundur, Gyllensten Ulf, Jacobs Kevin B, Shuldiner Alan R, Reinmaa Eva, Völzke Henry, Walker Mark, Wareham Nicholas J, Watkins Hugh, Wichmann H-Erich, Wilson James F, Zanen Pieter, Deloukas Panos, Heid Iris M, Lindgren Cecilia M, Mohlke Karen L, van der Harst Pim, Uusitupa Matti, Tuomilehto Jaakko, Ridker Paul M, Rivadeneira Fernando, Rotter Jerome I, Saaristo Timo E, Saleheen Danish, Schlessinger David, Slagboom P Eline, Snieder Harold, Spector Tim D, Strauch Konstantin, Stumvoll Michael, Speliotes Elizabeth K, Thorsteinsdottir Unnur, Barroso Inês, Price Alkes L, Lettre Guillaume, Loos Ruth J F, Weedon Michael N, Ingelsson Erik, O'Connell Jeffrey R, Abecasis Gonçalo R, Chasman Daniel I, Goddard Michael E, Visscher Peter M, Hirschhorn Joel N, Willer Cristen J, Franke Lude, van Duijn Cornelia M, Fox Caroline S, North Kari E, Strachan David P, Beckmann Jacques S, Berndt Sonja I, Boehnke Michael, Borecki Ingrid B, McCarthy Mark I, Metspalu Andres, Stefansson Kari, Uitterlinden André G, Frayling Timothy M, Rauramaa Rainer, Sinisalo Juha, Boerwinkle Eric, Bottinger Erwin P, Bouchard Claude, Cauchi Stéphane, Chambers John C, Chanock Stephen J, Cooper Richard S, de Bakker Paul I W, Dedoussis George, Ferrucci Luigi, Franks Paul W, Boehm Bernhard O, Bochud Murielle, Assimes Themistocles L, Steinthorsdottir Valgerdur, Stolk Ronald P, Tardif Jean-Claude, Tönjes Anke, Tremblay Angelo, Tremoli Elena, Virtamo Jarmo, Vohl Marie-Claude, Amouyel Philippe, Asselbergs Folkert W, Froguel Philippe, Groop Leif C, Haiman Christopher A, Moebus Susanne, Munroe Patricia B, Njølstad Inger, Oostra Ben A, Palmer Colin N A, Pedersen Nancy L, Perola Markus, Pérusse Louis, Peters Ulrike, Powell Joseph E, Power Chris, Melbye Mads, März Winfried, Martin Nicholas G, Hamsten Anders, Hayes M Geoffrey, Hui Jennie, Hunter David J, Hveem Kristian, Jukema J Wouter, Kaplan Robert C, Kivimäki Mika, Kuh Diana, Laakso Markku, Liu Yongmei, Quertermous Thomas, Nyholt Dale R, van Setten Jessica, van Vliet-Ostaptchouk Jana V, Wang Zhaoming, Yengo Loic, Zhang Weihua, Afzal Uzma, Arnlöv Johan, Arscott Gillian M, Bandinelli Stefania, Barrett Amy, Bellis Claire, van der Laan Sander W, Trompet Stella, Teumer Alexander, Palmer Cameron D, Pasko Dorota, Pechlivanis Sonali, Prokopenko Inga, Ried Janina S, Ripke Stephan, Shungin Dmitry, Stančáková Alena, Strawbridge Rona J, Sung Yun Ju, Tanaka Toshiko, Bennett Amanda J, Berne Christian, Blüher Matthias, Delgado Graciela, Denny Josh C, Dhonukshe-Rutten Rosalie, Dimitriou Maria, Doney Alex S F, Dörr Marcus, Eklund Niina, Eury Elodie, Folkersen Lasse, Garcia Melissa E, Geller Frank, Deelen Joris, De Jong Pim A, Daw E Warwick, Bolton Jennifer L, Böttcher Yvonne, Boyd Heather A, Bruinenberg Marcel, Buckley Brendan M, Buyske Steven, Caspersen Ida H, Chines Peter S, Clarke Robert, Claudi-Boehm Simone, Cooper Matthew, Giedraitis Vilmantas, Nalls Michael A, Wood Andrew R, Fall Tove, Fehrmann Rudolf, Ferreira Teresa, Jackson Anne U, Karjalainen Juha, Lo Ken Sin, Locke Adam E, Mägi Reedik, Mihailov Evelin, Porcu Eleonora, Randall Joshua C, Duan Yanan, Day Felix R, Croteau-Chonka Damien C, Esko Tõnu, Yang Jian, Vedantam Sailaja, Pers Tune H, Gustafsson Stefan, Chu Audrey Y, Estrada Karol, Luan Jian'an, Kutalik Zoltán, Amin Najaf, Buchkovich Martin L, Scherag André, Vinkhuyzen Anna A E, Westra Harm-Jan, Goel Anuj, Gong Jian, Justice Anne E, Kanoni Stavroula, Kleber Marcus E, Kristiansson Kati, Lim Unhee, Lotay Vaneet, Lui Julian C, Mangino Massimo, Mateo Leach Irene, Fraser Ross M, Fischer Krista, Feitosa Mary F, Winkler Thomas W, Workalemahu Tsegaselassie, Zhao Jing Hua, Absher Devin, Albrecht Eva, Anderson Denise, Baron Jeffrey, Beekman Marian, Demirkan Ayse, Ehret Georg B, Feenstra Bjarke, Medina-Gomez Carolina, Go Alan S, Monda Keri L, Roussel Ronan, Sanna Serena, Scharnagl Hubert, Scholtens Salome, Schumacher Fredrick R, Schunkert Heribert, Scott Robert A, Sehmi Joban, Seufferlein Thomas, Shi Jianxin, Silventoinen Karri, Rose Lynda M, Robertson Neil R, Renström Frida, Morken Mario A, Müller Gabriele, Müller-Nurasyid Martina, Musk Arthur W, Narisu Narisu, Nauck Matthias, Nolte Ilja M, Nöthen Markus M, Oozageer Laticia, Pilz Stefan, Rayner Nigel W, Smit Johannes H, Smith Albert Vernon, Smolonska Joanna, van Oort Floor V A, Vermeulen Sita H, Verweij Niek, Vonk Judith M, Waite Lindsay L, Waldenberger Melanie, Wennauer Roman, Wilkens Lynne R, Willenborg Christina, Wilsgaard Tom, Wojczynski Mary K, van Heemst Diana, van der Velde Nathalie, van Schoor Natasja M, Stanton Alice V, Stirrups Kathleen, Stott David J, Stringham Heather M, Sundstrom Johan, Swertz Morris A, Syvänen Ann-Christine, Tayo Bamidele O, Thorleifsson Gudmar, Tyrer Jonathan P, van Dijk Suzanne, Wong Andrew, Moayyeri Alireza, Grallert Harald, Helmer Quinta, Hemani Gibran, Henders Anjali K, Hillege Hans L, Hlatky Mark A, Hoffmann Wolfgang, Hoffmann Per, Holmen Oddgeir, Houwing-Duistermaat Jeanine J, Illig Thomas, Isaacs Aaron, Heard-Costa Nancy L, Hayward Caroline, Hassinen Maija, Grammer Tanja B, Gräßler Jürgen, Grönberg Henrik, de Groot Lisette C P G M, Groves Christopher J, Haessler Jeffrey, Hall Per, Haller Toomas, Hallmans Göran, Hannemann Anke, Hartman Catharina A, James Alan L, Jeff Janina, Johansen Berit, Lu Yingchang, Lyssenko Valeriya, Magnusson Patrik K E, Mahajan Anubha, Maillard Marc, McArdle Wendy L, McKenzie Colin A, McLachlan Stela, McLaren Paul J, Menni Cristina, Merger Sigrun, Lorentzon Mattias, Lobbens Stephane, Lindström Jaana, Johansson Åsa, Jolley Jennifer, Juliusdottir Thorhildur, Junttila Juhani, Kho Abel N, Kinnunen Leena, Klopp Norman, Kocher Thomas, Kratzer Wolfgang, Lichtner Peter, Lind Lars, Milani Lili

Citation

Jousilahti P, Lakka T, Langenberg C, Le Marchand L, Lehtimäki T, Lupoli S, Madden P, Männistö S, Manunta P, Marette A, Matise T, McKnight B, Kuusisto J, Kumari M, Kraja A, Jula A, Kaprio J, Kastelein J, Kayser M, Kee F, Keinanen-Kiukaanniemi S, Kiemeney L, Kooner J, Kooperberg C, Koskinen S, Kovacs P, Meitinger T, Moll F, Montgomery G, Rankinen T, Rao D, Rice T, Ritchie M, Rudan I, Salomaa V, Samani N, Saramies J, Sarzynski M, Schwarz P, Sebert S, Raitakari O, Qi L, Price J, Morris A, Morris A, Murray J, Nelis M, Ohlsson C, Oldehinkel A, Ong K, Ouwehand W, Pasterkamp G, Peters A, Pramstaller P, Sever P, Jarvelin M, Wright A, Caulfield M, Chakravarti A, Collins R, Collins F, Crawford D, Cupples L, Danesh J, de Faire U, den Ruijter H, Erbel R, Erdmann J, Campbell H, Brown M, Brambilla P, Zhang Q, Arveiler D, Bakker S, Beilby J, Bergman R, Bergmann S, Biffar R, Blangero J, Boomsma D, Bornstein S, Bovet P, Eriksson J, Farrall M, Ferrannini E, Hattersley A, Heath A, Hengstenberg C, Hicks A, Hindorff L, Hingorani A, Hofman A, Hovingh G, Humphries S, Hunt S, Hyppönen E, Harris T, Hall A, Haas D, Ferrieres J, Ford I, Forouhi N, Forrester T, Gansevoort R, Gejman P, Gieger C, Golay A, Gottesman O, Gudnason V, Gyllensten U, Jacobs K, Shuldiner A, Reinmaa E, Völzke H, Walker M, Wareham N, Watkins H, Wichmann H, Wilson J, Zanen P, Deloukas P, Heid I, Lindgren C, Mohlke K, van der Harst P, Uusitupa M, Tuomilehto J, Ridker P, Rivadeneira F, Rotter J, Saaristo T, Saleheen D, Schlessinger D, Slagboom P, Snieder H, Spector T, Strauch K, Stumvoll M, Speliotes E, Thorsteinsdottir U, Barroso I, Price A, Lettre G, Loos R, Weedon M, Ingelsson E, O'Connell J, Abecasis G, Chasman D, Goddard M, Visscher P, Hirschhorn J, Willer C, Franke L, van Duijn C, Fox C, North K, Strachan D, Beckmann J, Berndt S, Boehnke M, Borecki I, McCarthy M, Metspalu A, Stefansson K, Uitterlinden A, Frayling T, Rauramaa R, Sinisalo J, Boerwinkle E, Bottinger E, Bouchard C, Cauchi S, Chambers J, Chanock S, Cooper R, de Bakker P, Dedoussis G, Ferrucci L, Franks P, Boehm B, Bochud M, Assimes T, Steinthorsdottir V, Stolk R, Tardif J, Tönjes A, Tremblay A, Tremoli E, Virtamo J, Vohl M, Amouyel P, Asselbergs F, Froguel P, Groop L, Haiman C, Moebus S, Munroe P, Njølstad I, Oostra B, Palmer C, Pedersen N, Perola M, Pérusse L, Peters U, Powell J, Power C, Melbye M, März W, Martin N, Hamsten A, Hayes M, Hui J, Hunter D, Hveem K, Jukema J, Kaplan R, Kivimäki M, Kuh D, Laakso M, Liu Y, Quertermous T, Nyholt D, van Setten J, van Vliet-Ostaptchouk J, Wang Z, Yengo L, Zhang W, Afzal U, Arnlöv J, Arscott G, Bandinelli S, Barrett A, Bellis C, van der Laan S, Trompet S, Teumer A, Palmer C, Pasko D, Pechlivanis S, Prokopenko I, Ried J, Ripke S, Shungin D, Stančáková A, Strawbridge R, Sung Y, Tanaka T, Bennett A, Berne C, Blüher M, Delgado G, Denny J, Dhonukshe-Rutten R, Dimitriou M, Doney A, Dörr M, Eklund N, Eury E, Folkersen L, Garcia M, Geller F, Deelen J, De Jong P, Daw E, Bolton J, Böttcher Y, Boyd H, Bruinenberg M, Buckley B, Buyske S, Caspersen I, Chines P, Clarke R, Claudi-Boehm S, Cooper M, Giedraitis V, Nalls M, Wood A, Fall T, Fehrmann R, Ferreira T, Jackson A, Karjalainen J, Lo K, Locke A, Mägi R, Mihailov E, Porcu E, Randall J, Duan Y, Day F, Croteau-Chonka D, Esko T, Yang J, Vedantam S, Pers T, Gustafsson S, Chu A, Estrada K, Luan J, Kutalik Z, Amin N, Buchkovich M, Scherag A, Vinkhuyzen A, Westra H, Goel A, Gong J, Justice A, Kanoni S, Kleber M, Kristiansson K, Lim U, Lotay V, Lui J, Mangino M, Mateo Leach I, Fraser R, Fischer K, Feitosa M, Winkler T, Workalemahu T, Zhao J, Absher D, Albrecht E, Anderson D, Baron J, Beekman M, Demirkan A, Ehret G, Feenstra B, Medina-Gomez C, Go A, Monda K, Roussel R, Sanna S, Scharnagl H, Scholtens S, Schumacher F, Schunkert H, Scott R, Sehmi J, Seufferlein T, Shi J, Silventoinen K, Rose L, Robertson N, Renström F, Morken M, Müller G, Müller-Nurasyid M, Musk A, Narisu N, Nauck M, Nolte I, Nöthen M, Oozageer L, Pilz S, Rayner N, Smit J, Smith A, Smolonska J, van Oort F, Vermeulen S, Verweij N, Vonk J, Waite L, Waldenberger M, Wennauer R, Wilkens L, Willenborg C, Wilsgaard T, Wojczynski M, van Heemst D, van der Velde N, van Schoor N, Stanton A, Stirrups K, Stott D, Stringham H, Sundstrom J, Swertz M, Syvänen A, Tayo B, Thorleifsson G, Tyrer J, van Dijk S, Wong A, Moayyeri A, Grallert H, Helmer Q, Hemani G, Henders A, Hillege H, Hlatky M, Hoffmann W, Hoffmann P, Holmen O, Houwing-Duistermaat J, Illig T, Isaacs A, Heard-Costa N, Hayward C, Hassinen M, Grammer T, Gräßler J, Grönberg H, de Groot L, Groves C, Haessler J, Hall P, Haller T, Hallmans G, Hannemann A, Hartman C, James A, Jeff J, Johansen B, Lu Y, Lyssenko V, Magnusson P, Mahajan A, Maillard M, McArdle W, McKenzie C, McLachlan S, McLaren P, Menni C, Merger S, Lorentzon M, Lobbens S, Lindström J, Johansson Å, Jolley J, Juliusdottir T, Junttila J, Kho A, Kinnunen L, Klopp N, Kocher T, Kratzer W, Lichtner P, Lind L, Milani L. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet 2014; 46:1173-86.

Type

Journal Paper/Review (English)

Journal

Nat Genet 2014; 46

Publication Date

Oct 5, 2014

Issn Electronic

1546-1718

Pages

1173-86

Brief description/objective

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.