Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Wood, Andrew R ; Esko, Tonu ; Yang, Jian ; Vedantam, Sailaja ; Pers, Tune H ; Gustafsson, Stefan ; Chu, Audrey Y ; Estrada, Karol ; Luan, Jian'an and Kutalik, Zoltán , et al. (2014) In Nature Genetics 46(11). p.1173-1186
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
46
issue
11
pages
1173 - 1186
publisher
Nature Publishing Group
external identifiers
  • pmid:25282103
  • wos:000344131900008
  • scopus:84908890496
  • pmid:25282103
ISSN
1546-1718
DOI
10.1038/ng.3097
language
English
LU publication?
yes
id
3eef2a04-5cff-4954-bb97-af39afe17a15 (old id 4737727)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25282103?dopt=Abstract
date added to LUP
2016-04-01 10:23:36
date last changed
2022-04-27 21:18:33
@article{3eef2a04-5cff-4954-bb97-af39afe17a15,
  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.}},
  author       = {{Wood, Andrew R and Esko, Tonu and Yang, Jian and Vedantam, Sailaja and Pers, Tune H and Gustafsson, Stefan and Chu, Audrey Y and Estrada, Karol and Luan, Jian'an and Kutalik, Zoltán and Amin, Najaf and Buchkovich, Martin L and Croteau-Chonka, Damien C and Day, Felix R and Duan, Yanan and Fall, Tove and Fehrmann, Rudolf and Ferreira, Teresa and Jackson, Anne U and Karjalainen, Juha and Lo, Ken Sin and Locke, Adam E and Mägi, Reedik and Mihailov, Evelin and Porcu, Eleonora and Randall, Joshua C and Scherag, André and Vinkhuyzen, Anna A E and Westra, Harm-Jan and Winkler, Thomas W and Workalemahu, Tsegaselassie and Zhao, Jing Hua and Absher, Devin and Albrecht, Eva and Anderson, Denise and Baron, Jeffrey and Beekman, Marian and Demirkan, Ayse and Ehret, Georg B and Feenstra, Bjarke and Feitosa, Mary F and Fischer, Krista and Fraser, Ross M and Goel, Anuj and Gong, Jian and Justice, Anne E and Kanoni, Stavroula and Kleber, Marcus E and Kristiansson, Kati and Lim, Unhee and Lotay, Vaneet and Lui, Julian C and Mangino, Massimo and Mateo Leach, Irene and Medina-Gomez, Carolina and Nalls, Michael A and Nyholt, Dale R and Palmer, Cameron D and Pasko, Dorota and Pechlivanis, Sonali and Prokopenko, Inga and Ried, Janina S and Ripke, Stephan and Shungin, Dmitry and Stancáková, Alena and Strawbridge, Rona J and Sung, Yun Ju and Tanaka, Toshiko and Teumer, Alexander and Trompet, Stella and van der Laan, Sander W and van Setten, Jessica and Van Vliet-Ostaptchouk, Jana V and Wang, Zhaoming and Yengo, Loïc and Zhang, Weihua and Afzal, Uzma and Arnlöv, Johan and Arscott, Gillian M and Bandinelli, Stefania and Barrett, Amy and Bellis, Claire and Bennett, Amanda J and Berne, Christian and Blüher, Matthias and Bolton, Jennifer L and Böttcher, Yvonne and Boyd, Heather A and Bruinenberg, Marcel and Buckley, Brendan M and Buyske, Steven and Caspersen, Ida H and Chines, Peter S and Clarke, Robert and Claudi-Boehm, Simone and Cooper, Matthew and Daw, E Warwick and De Jong, Pim A and Deelen, Joris and Delgado, Graciela and Denny, Josh C and Dhonukshe-Rutten, Rosalie and Dimitriou, Maria and Doney, Alex S F and Dörr, Marcus and Eklund, Niina and Eury, Elodie and Folkersen, Lasse and Garcia, Melissa E and Geller, Frank and Giedraitis, Vilmantas and Go, Alan S and Grallert, Harald and Grammer, Tanja B and Gräßler, Jürgen and Grönberg, Henrik and de Groot, Lisette C P G M and Groves, Christopher J and Haessler, Jeffrey and Hall, Per and Haller, Toomas and Hallmans, Goran and Hannemann, Anke and Hartman, Catharina A and Hassinen, Maija and Hayward, Caroline and Heard-Costa, Nancy L and Helmer, Quinta and Hemani, Gibran and Henders, Anjali K and Hillege, Hans L and Hlatky, Mark A and Hoffmann, Wolfgang and Hoffmann, Per and Holmen, Oddgeir and Houwing-Duistermaat, Jeanine J and Illig, Thomas and Isaacs, Aaron and James, Alan L and Jeff, Janina and Johansen, Berit and Johansson, Asa and Jolley, Jennifer and Juliusdottir, Thorhildur and Junttila, Juhani and Kho, Abel N and Kinnunen, Leena and Klopp, Norman and Kocher, Thomas and Kratzer, Wolfgang and Lichtner, Peter and Lind, Lars and Lindström, Jaana and Lobbens, Stéphane and Lorentzon, Mattias and Lu, Yingchang and Lyssenko, Valeriya and Magnusson, Patrik K E and Mahajan, Anubha and Maillard, Marc and McArdle, Wendy L and McKenzie, Colin A and McLachlan, Stela and McLaren, Paul J and Menni, Cristina and Merger, Sigrun and Milani, Lili and Moayyeri, Alireza and Monda, Keri L and Morken, Mario A and Müller, Gabriele and Müller-Nurasyid, Martina and Musk, Arthur W and Narisu, Narisu and Nauck, Matthias and Nolte, Ilja M and Nöthen, Markus M and Oozageer, Laticia and Pilz, Stefan and Rayner, Nigel W and Renström, Frida and Robertson, Neil R and Rose, Lynda M and Roussel, Ronan and Sanna, Serena and Scharnagl, Hubert and Scholtens, Salome and Schumacher, Fredrick R and Schunkert, Heribert and Scott, Robert A and Sehmi, Joban and Seufferlein, Thomas and Shi, Jianxin and Silventoinen, Karri and Smit, Johannes H and Smith, Albert Vernon and Smolonska, Joanna and Stanton, Alice V and Stirrups, Kathleen and Stott, David J and Stringham, Heather M and Sundström, Johan and Swertz, Morris A and Syvänen, Ann-Christine and Tayo, Bamidele O and Thorleifsson, Gudmar and Tyrer, Jonathan P and van Dijk, Suzanne and van Schoor, Natasja M and van der Velde, Nathalie and van Heemst, Diana and van Oort, Floor V A and Vermeulen, Sita H and Verweij, Niek and Vonk, Judith M and Waite, Lindsay L and Waldenberger, Melanie and Wennauer, Roman and Wilkens, Lynne R and Willenborg, Christina and Wilsgaard, Tom and Wojczynski, Mary K and Wong, Andrew and Wright, Alan F and Zhang, Qunyuan and Arveiler, Dominique and Bakker, Stephan J L and Beilby, John and Bergman, Richard N and Bergmann, Sven and Biffar, Reiner and Blangero, John and Boomsma, Dorret I and Bornstein, Stefan R and Bovet, Pascal and Brambilla, Paolo and Brown, Morris J and Campbell, Harry and Caulfield, Mark J and Chakravarti, Aravinda and Collins, Rory and Collins, Francis S and Crawford, Dana C and Cupples, L Adrienne and Danesh, John and de Faire, Ulf and den Ruijter, Hester M and Erbel, Raimund and Erdmann, Jeanette and Eriksson, Johan G and Farrall, Martin and Ferrannini, Ele and Ferrières, Jean and Ford, Ian and Forouhi, Nita G and Forrester, Terrence and Gansevoort, Ron T and Gejman, Pablo V and Gieger, Christian and Golay, Alain and Gottesman, Omri and Gudnason, Vilmundur and Gyllensten, Ulf and Haas, David W and Hall, Alistair S and Harris, Tamara B and Hattersley, Andrew T and Heath, Andrew C and Hengstenberg, Christian and Hicks, Andrew A and Hindorff, Lucia A and Hingorani, Aroon D and Hofman, Albert and Hovingh, G Kees and Humphries, Steve E and Hunt, Steven C and Hypponen, Elina and Jacobs, Kevin B and Jarvelin, Marjo-Riitta and Jousilahti, Pekka and Jula, Antti M and Kaprio, Jaakko and Kastelein, John J P and Kayser, Manfred and Kee, Frank and Keinanen-Kiukaanniemi, Sirkka M and Kiemeney, Lambertus A and Kooner, Jaspal S and Kooperberg, Charles and Koskinen, Seppo and Kovacs, Peter and Kraja, Aldi T and Kumari, Meena and Kuusisto, Johanna and Lakka, Timo A and Langenberg, Claudia and Le Marchand, Loic and Lehtimäki, Terho and Lupoli, Sara and Madden, Pamela A F and Männistö, Satu and Manunta, Paolo and Marette, André and Matise, Tara C and McKnight, Barbara and Meitinger, Thomas and Moll, Frans L and Montgomery, Grant W and Morris, Andrew D and Morris, Andrew P and Murray, Jeffrey C and Nelis, Mari and Ohlsson, Claes and Oldehinkel, Albertine J and Ong, Ken K and Ouwehand, Willem H and Pasterkamp, Gerard and Peters, Annette and Pramstaller, Peter P and Price, Jackie F and Qi, Lu and Raitakari, Olli T and Rankinen, Tuomo and Rao, D C and Rice, Treva K and Ritchie, Marylyn and Rudan, Igor and Salomaa, Veikko and Samani, Nilesh J and Saramies, Jouko and Sarzynski, Mark A and Schwarz, Peter E H and Sebert, Sylvain and Sever, Peter and Shuldiner, Alan R and Sinisalo, Juha and Steinthorsdottir, Valgerdur and Stolk, Ronald P and Tardif, Jean-Claude and Tönjes, Anke and Tremblay, Angelo and Tremoli, Elena and Virtamo, Jarmo and Vohl, Marie-Claude and Amouyel, Philippe and Asselbergs, Folkert W and Assimes, Themistocles L and Bochud, Murielle and Boehm, Bernhard O and Boerwinkle, Eric and Bottinger, Erwin P and Bouchard, Claude and Cauchi, Stéphane and Chambers, John C and Chanock, Stephen J and Cooper, Richard S and de Bakker, Paul I W and Dedoussis, George and Ferrucci, Luigi and Franks, Paul and Froguel, Philippe and Groop, Leif and Haiman, Christopher A and Hamsten, Anders and Hayes, M Geoffrey and Hui, Jennie and Hunter, David J and Hveem, Kristian and Jukema, J Wouter and Kaplan, Robert C and Kivimaki, Mika and Kuh, Diana and Laakso, Markku and Liu, Yongmei and Martin, Nicholas G and März, Winfried and Melbye, Mads and Moebus, Susanne and Munroe, Patricia B and Njølstad, Inger and Oostra, Ben A and Palmer, Colin N A and Pedersen, Nancy L and Perola, Markus and Pérusse, Louis and Peters, Ulrike and Powell, Joseph E and Power, Chris and Quertermous, Thomas and Rauramaa, Rainer and Reinmaa, Eva and Ridker, Paul M and Rivadeneira, Fernando and Rotter, Jerome I and Saaristo, Timo E and Saleheen, Danish and Schlessinger, David and Slagboom, P Eline and Snieder, Harold and Spector, Tim D and Strauch, Konstantin and Stumvoll, Michael and Tuomilehto, Jaakko and Uusitupa, Matti and van der Harst, Pim and Völzke, Henry and Walker, Mark and Wareham, Nicholas J and Watkins, Hugh and Wichmann, H-Erich and Wilson, James F and Zanen, Pieter and Deloukas, Panos and Heid, Iris M and Lindgren, Cecilia M and Mohlke, Karen L and Speliotes, Elizabeth K and Thorsteinsdottir, Unnur and Barroso, Inês and Fox, Caroline S and North, Kari E and Strachan, David P and Beckmann, Jacques S and Berndt, Sonja I and Boehnke, Michael and Borecki, Ingrid B and McCarthy, Mark I and Metspalu, Andres and Stefansson, Kari and Uitterlinden, André G and van Duijn, Cornelia M and Franke, Lude and Willer, Cristen J and Price, Alkes L and Lettre, Guillaume and Loos, Ruth J F and Weedon, Michael N and Ingelsson, Erik and O'Connell, Jeffrey R and Abecasis, Goncalo R and Chasman, Daniel I and Goddard, Michael E and Visscher, Peter M and Hirschhorn, Joel N and Frayling, Timothy M}},
  issn         = {{1546-1718}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1173--1186}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Defining the role of common variation in the genomic and biological architecture of adult human height.}},
  url          = {{http://dx.doi.org/10.1038/ng.3097}},
  doi          = {{10.1038/ng.3097}},
  volume       = {{46}},
  year         = {{2014}},
}