Defining the role of common variation in the genomic and biological architecture of adult human height.
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Authors
Wood, Andrew REsko, Tonu
Yang, Jian
Vedantam, Sailaja
Pers, Tune H
Gustafsson, Stefan
Chu, Audrey Y
Estrada, Karol
Luan, Jian'an
Kutalik, Zoltán
Amin, Najaf
Buchkovich, Martin L
Croteau-Chonka, Damien C
Day, Felix R
Duan, Yanan
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
Scherag, André
Vinkhuyzen, Anna A E
Westra, Harm-Jan
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
Feitosa, Mary F
Fischer, Krista
Fraser, Ross M
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
Medina-Gomez, Carolina
Nalls, Michael A
Nyholt, Dale R
Palmer, Cameron D
Pasko, Dorota
Pechlivanis, Sonali
Prokopenko, Inga
Ried, Janina S
Ripke, Stephan
Shungin, Dmitry
Stancáková, Alena
Strawbridge, Rona J
Sung, Yun Ju
Tanaka, Toshiko
Teumer, Alexander
Trompet, Stella
van der Laan, Sander W
van Setten, Jessica
Van Vliet-Ostaptchouk, Jana V
Wang, Zhaoming
Yengo, Loïc
Zhang, Weihua
Afzal, Uzma
Arnlöv, Johan
Arscott, Gillian M
Bandinelli, Stefania
Barrett, Amy
Bellis, Claire
Bennett, Amanda J
Berne, Christian
Blüher, Matthias
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
Daw, E Warwick
De Jong, Pim A
Deelen, Joris
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
Giedraitis, Vilmantas
Go, Alan S
Grallert, Harald
Grammer, Tanja B
Gräßler, Jürgen
Grönberg, Henrik
de Groot, Lisette C P G M
Groves, Christopher J
Haessler, Jeffrey
Hall, Per
Haller, Toomas
Hallmans, Goran
Hannemann, Anke
Hartman, Catharina A
Hassinen, Maija
Hayward, Caroline
Heard-Costa, Nancy L
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
James, Alan L
Jeff, Janina
Johansen, Berit
Johansson, Åsa
Jolley, Jennifer
Juliusdottir, Thorhildur
Junttila, Juhani
Kho, Abel N
Kinnunen, Leena
Klopp, Norman
Kocher, Thomas
Kratzer, Wolfgang
Lichtner, Peter
Lind, Lars
Lindström, Jaana
Lobbens, Stéphane
Lorentzon, Mattias
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
Milani, Lili
Moayyeri, Alireza
Monda, Keri L
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
Renstrom, Frida
Robertson, Neil R
Rose, Lynda M
Roussel, Ronan
Sanna, Serena
Scharnagl, Hubert
Scholtens, Salome
Schumacher, Fredrick R
Schunkert, Heribert
Scott, Robert A
Sehmi, Joban
Seufferlein, Thomas
Shi, Jianxin
Silventoinen, Karri
Smit, Johannes H
Smith, Albert Vernon
Smolonska, Joanna
Stanton, Alice V
Stirrups, Kathleen
Stott, David J
Stringham, Heather M
Sundström, Johan
Swertz, Morris A
Syvänen, Ann-Christine
Tayo, Bamidele O
Thorleifsson, Gudmar
Tyrer, Jonathan P
van Dijk, Suzanne
van Schoor, Natasja M
van der Velde, Nathalie
van Heemst, Diana
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
Wong, Andrew
Wright, Alan F
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
Brambilla, Paolo
Brown, Morris J
Campbell, Harry
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
Eriksson, Johan G
Farrall, Martin
Ferrannini, Ele
Ferrières, Jean
Ford, Ian
Forouhi, Nita G
Forrester, Terrence
Gansevoort, Ron T
Gejman, Pablo V
Gieger, Christian
Golay, Alain
Gottesman, Omri
Gudnason, Vilmundur
Gyllensten, Ulf
Haas, David W
Hall, Alistair S
Harris, Tamara B
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
Hypponen, Elina
Jacobs, Kevin B
Jarvelin, Marjo-Riitta
Jousilahti, Pekka
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
Kraja, Aldi T
Kumari, Meena
Kuusisto, Johanna
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
Meitinger, Thomas
Moll, Frans L
Montgomery, Grant W
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
Price, Jackie F
Qi, Lu
Raitakari, Olli T
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
Sever, Peter
Shuldiner, Alan R
Sinisalo, Juha
Steinthorsdottir, Valgerdur
Stolk, Ronald P
Tardif, Jean-Claude
Tönjes, Anke
Tremblay, Angelo
Tremoli, Elena
Virtamo, Jarmo
Vohl, Marie-Claude
Amouyel, Philippe
Asselbergs, Folkert W
Assimes, Themistocles L
Bochud, Murielle
Boehm, Bernhard O
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
Froguel, Philippe
Groop, Leif C
Haiman, Christopher A
Hamsten, Anders
Hayes, M Geoffrey
Hui, Jennie
Hunter, David J
Hveem, Kristian
Jukema, J Wouter
Kaplan, Robert C
Kivimaki, Mika
Kuh, Diana
Laakso, Markku
Liu, Yongmei
Martin, Nicholas G
März, Winfried
Melbye, Mads
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
Quertermous, Thomas
Rauramaa, Rainer
Reinmaa, Eva
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
Tuomilehto, Jaakko
Uusitupa, Matti
van der Harst, Pim
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
Speliotes, Elizabeth K
Thorsteinsdottir, Unnur
Barroso, Inês
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
van Duijn, Cornelia M
Franke, Lude
Willer, Cristen J
Price, Alkes L
Lettre, Guillaume
Loos, Ruth J F
Weedon, Michael N
Ingelsson, Erik
O'Connell, Jeffrey R
Abecasis, Goncalo R
Chasman, Daniel I
Goddard, Michael E
Visscher, Peter M
Hirschhorn, Joel N
Frayling, Timothy M
Issue Date
2014-11
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Nat. Genet. 2014, 46 (11):1173-86Abstract
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.Description
To access publisher's full text version of this article click on the hyperlink at the bottom of the pageAdditional Links
http://dx.doi.org/ 10.1038/ng.3097http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4250049/
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Archived with thanks to Nature geneticsae974a485f413a2113503eed53cd6c53
10.1038/ng.3097
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