Abstract
To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102 -11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10 -8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
| Original language | English (US) |
|---|---|
| Article number | e1000508 |
| Journal | PLoS genetics |
| Volume | 5 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2009 |
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Molecular Biology
- Genetics
- Genetics(clinical)
- Cancer Research
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Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. / Lindgren, Cecilia M.; Heid, Iris M.; Randall, Joshua C.; Lamina, Claudia; Steinthorsdottir, Valgerdur; Qi, Lu; Speliotes, Elizabeth K.; Thorleifsson, Gudmar; Willer, Cristen J.; Herrera, Blanca M.; Jackson, Anne U.; Lim, Noha; Scheet, Paul; Soranzo, Nicole; Amin, Najaf; Aulchenko, Yurii S.; Chambers, John C.; Drong, Alexander; Luan, Jia N.an; Lyon, Helen N.; Rivadeneira, Fernando; Sanna, Serena; Timpson, Nicholas J.; Zillikens, M. Carola; Jing, Hua Zhao; Almgren, Peter; Bandinelli, Stefania; Bennett, Amanda J.; Bergman, Richard N.; Bonnycastle, Lori L.; Bumpstead, Suzannah J.; Chanock, Stephen J.; Cherkas, Lynn; Chines, Peter; Coin, Lachlan; Cooper, Cyrus; Crawford, Gabriel; Doering, Angela; Dominiczak, Anna; Doney, Alex S.F.; Ebrahim, Shah; Elliott, Paul; Erdos, Michael R.; Estrada, Karol; Ferrucci, Luigi; Fischer, Guido; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Groves, Christopher J.; Grundy, Scott; Guiducci, Candace; Hadley, David; Hamsten, Anders; Havulinna, Aki S.; Hofman, Albert; Holle, Rolf; Holloway, John W.; Illig, Thomas; Isomaa, Bo; Jacobs, Leonie C.; Jameson, Karen; Jousilahti, Pekka; Karpe, Fredrik; Kuusisto, Johanna; Laitinen, Jaana; Lathrop, G. Mark; Lawlor, Debbie A.; Mangino, Massimo; McArdle, Wendy L.; Meitinger, Thomas; Morken, Mario A.; Morris, Andrew P.; Munroe, Patricia; Narisu, Narisu; Nordström, Anna; Nordström, Peter; Oostra, Ben A.; Palmer, Colin N.A.; Payne, Felicity; Peden, John F.; Prokopenko, Inga; Renström, Frida; Ruokonen, Aimo; Salomaa, Veikko; Sandhu, Manjinder S.; Scott, Laura J.; Scuteri, Angelo; Silander, Kaisa; Song, Kijoung; Yuan, Xin; Stringham, Heather M.; Swift, Amy J.; Tuomi, Tiinamaija; Uda, Manuela; Vollenweider, Peter; Waeber, Gerard; Wallace, Chris; Walters, G. Bragi; Weedon, Michael N.; Witteman, Jacqueline C.M.; Zhang, Cuilin; Zhang, Weihua; Caulfield, Mark J.; Collins, Francis S.; Smith, George Davey; Day, Ian N.M.; Franks, Paul W.; Hattersley, Andrew T.; Hu, Frank B.; Jarvelin, Marjo Riitta; Kong, Augustine; Kooner, Jaspal S.; Laakso, Markku; Lakatta, Edward; Mooser, Vincent; Morris, Andrew D.; Peltonen, Leena; Samani, Nilesh J.; Spector, Timothy D.; Strachan, David P.; Tanaka, Toshiko; Tuomilehto, Jaakko; Uitterlinden, André G.; Van Duijn, Cornelia M.; Wareham, Nicholas J.; Watkins, Hugh; Waterworth, Dawn M.; Boehnke, Michael; Deloukas, Panos; Groop, Leif; Hunter, David J.; Thorsteinsdottir, Unnur; Schlessinger, David; Wichmann, H. Erich; Frayling, Timothy M.; Abecasis, Gonçalo R.; Hirschhorn, Joel N.; Loos, Ruth J.F.; Stefansson, Kari; Mohlke, Karen L.; Barroso, Inês; McCarthy, Mark I.
In: PLoS genetics, Vol. 5, No. 6, e1000508, 06.2009.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution
AU - Lindgren, Cecilia M.
AU - Heid, Iris M.
AU - Randall, Joshua C.
AU - Lamina, Claudia
AU - Steinthorsdottir, Valgerdur
AU - Qi, Lu
AU - Speliotes, Elizabeth K.
AU - Thorleifsson, Gudmar
AU - Willer, Cristen J.
AU - Herrera, Blanca M.
AU - Jackson, Anne U.
AU - Lim, Noha
AU - Scheet, Paul
AU - Soranzo, Nicole
AU - Amin, Najaf
AU - Aulchenko, Yurii S.
AU - Chambers, John C.
AU - Drong, Alexander
AU - Luan, Jia N.an
AU - Lyon, Helen N.
AU - Rivadeneira, Fernando
AU - Sanna, Serena
AU - Timpson, Nicholas J.
AU - Zillikens, M. Carola
AU - Jing, Hua Zhao
AU - Almgren, Peter
AU - Bandinelli, Stefania
AU - Bennett, Amanda J.
AU - Bergman, Richard N.
AU - Bonnycastle, Lori L.
AU - Bumpstead, Suzannah J.
AU - Chanock, Stephen J.
AU - Cherkas, Lynn
AU - Chines, Peter
AU - Coin, Lachlan
AU - Cooper, Cyrus
AU - Crawford, Gabriel
AU - Doering, Angela
AU - Dominiczak, Anna
AU - Doney, Alex S.F.
AU - Ebrahim, Shah
AU - Elliott, Paul
AU - Erdos, Michael R.
AU - Estrada, Karol
AU - Ferrucci, Luigi
AU - Fischer, Guido
AU - Forouhi, Nita G.
AU - Gieger, Christian
AU - Grallert, Harald
AU - Groves, Christopher J.
AU - Grundy, Scott
AU - Guiducci, Candace
AU - Hadley, David
AU - Hamsten, Anders
AU - Havulinna, Aki S.
AU - Hofman, Albert
AU - Holle, Rolf
AU - Holloway, John W.
AU - Illig, Thomas
AU - Isomaa, Bo
AU - Jacobs, Leonie C.
AU - Jameson, Karen
AU - Jousilahti, Pekka
AU - Karpe, Fredrik
AU - Kuusisto, Johanna
AU - Laitinen, Jaana
AU - Lathrop, G. Mark
AU - Lawlor, Debbie A.
AU - Mangino, Massimo
AU - McArdle, Wendy L.
AU - Meitinger, Thomas
AU - Morken, Mario A.
AU - Morris, Andrew P.
AU - Munroe, Patricia
AU - Narisu, Narisu
AU - Nordström, Anna
AU - Nordström, Peter
AU - Oostra, Ben A.
AU - Palmer, Colin N.A.
AU - Payne, Felicity
AU - Peden, John F.
AU - Prokopenko, Inga
AU - Renström, Frida
AU - Ruokonen, Aimo
AU - Salomaa, Veikko
AU - Sandhu, Manjinder S.
AU - Scott, Laura J.
AU - Scuteri, Angelo
AU - Silander, Kaisa
AU - Song, Kijoung
AU - Yuan, Xin
AU - Stringham, Heather M.
AU - Swift, Amy J.
AU - Tuomi, Tiinamaija
AU - Uda, Manuela
AU - Vollenweider, Peter
AU - Waeber, Gerard
AU - Wallace, Chris
AU - Walters, G. Bragi
AU - Weedon, Michael N.
AU - Witteman, Jacqueline C.M.
AU - Zhang, Cuilin
AU - Zhang, Weihua
AU - Caulfield, Mark J.
AU - Collins, Francis S.
AU - Smith, George Davey
AU - Day, Ian N.M.
AU - Franks, Paul W.
AU - Hattersley, Andrew T.
AU - Hu, Frank B.
AU - Jarvelin, Marjo Riitta
AU - Kong, Augustine
AU - Kooner, Jaspal S.
AU - Laakso, Markku
AU - Lakatta, Edward
AU - Mooser, Vincent
AU - Morris, Andrew D.
AU - Peltonen, Leena
AU - Samani, Nilesh J.
AU - Spector, Timothy D.
AU - Strachan, David P.
AU - Tanaka, Toshiko
AU - Tuomilehto, Jaakko
AU - Uitterlinden, André G.
AU - Van Duijn, Cornelia M.
AU - Wareham, Nicholas J.
AU - Watkins, Hugh
AU - Waterworth, Dawn M.
AU - Boehnke, Michael
AU - Deloukas, Panos
AU - Groop, Leif
AU - Hunter, David J.
AU - Thorsteinsdottir, Unnur
AU - Schlessinger, David
AU - Wichmann, H. Erich
AU - Frayling, Timothy M.
AU - Abecasis, Gonçalo R.
AU - Hirschhorn, Joel N.
AU - Loos, Ruth J.F.
AU - Stefansson, Kari
AU - Mohlke, Karen L.
AU - Barroso, Inês
AU - McCarthy, Mark I.
PY - 2009/6
Y1 - 2009/6
N2 - To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102 -11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10 -8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
AB - To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102 -11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10 -8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
UR - http://www.scopus.com/inward/record.url?scp=67651236725&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67651236725&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1000508
DO - 10.1371/journal.pgen.1000508
M3 - Article
C2 - 19557161
AN - SCOPUS:67651236725
VL - 5
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 6
M1 - e1000508
ER -