Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Cecilia M. Lindgren; Iris M. Heid; groep; Joshua C. Randall; Claudia Lamina; Valgerdur Steinthorsdottir; Lu Qi; Elizabeth K. Speliotes; Gudmar Thorleifsson; Cristen J. Willer; Blanca M. Herrera; Anne U. Jackson; Noha Lim; Paul Scheet; Nicole Soranzo; Najaf Amin; Yurii S. Aulchenko; John C. Chambers; Alexander Drong; Jia N.an Luan; Helen N. Lyon; Fernando Rivadeneira; Serena Sanna; Nicholas J. Timpson; M. Carola Zillikens; Hua Zhao Jing; Peter Almgren; Stefania Bandinelli; Amanda J. Bennett; Richard N. Bergman; Lori L. Bonnycastle; Suzannah J. Bumpstead; Stephen J. Chanock; Lynn Cherkas; Peter Chines; Lachlan Coin; Cyrus Cooper; Gabriel Crawford; Angela Doering; Anna Dominiczak; Alex S.F. Doney; Shah Ebrahim; Paul Elliott; Michael R. Erdos; Karol Estrada; Luigi Ferrucci; Albert Hofman; Leonie C. Jacobs; Ben A. Oostra; André G. Uitterlinden; Cornelia M. Van Duijn

doi:10.1371/journal.pgen.1000508

Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Cecilia M. Lindgren
, Iris M. Heid
, groep
, Joshua C. Randall
, Claudia Lamina
, Valgerdur Steinthorsdottir
, Lu Qi
, Elizabeth K. Speliotes
, Gudmar Thorleifsson
, Cristen J. Willer
, Blanca M. Herrera
, Anne U. Jackson
, Noha Lim
, Paul Scheet
, Nicole Soranzo
, Najaf Amin
, Yurii S. Aulchenko
, John C. Chambers
, Alexander Drong
, Jia N.an Luan

Helen N. Lyon, Fernando Rivadeneira, Serena Sanna, Nicholas J. Timpson, M. Carola Zillikens, Hua Zhao Jing, Peter Almgren, Stefania Bandinelli, Amanda J. Bennett, Richard N. Bergman, Lori L. Bonnycastle, Suzannah J. Bumpstead, Stephen J. Chanock, Lynn Cherkas, Peter Chines, Lachlan Coin, Cyrus Cooper, Gabriel Crawford, Angela Doering, Anna Dominiczak, Alex S.F. Doney, Shah Ebrahim, Paul Elliott, Michael R. Erdos, Karol Estrada, Luigi Ferrucci, Albert Hofman, Leonie C. Jacobs, Ben A. Oostra, André G. Uitterlinden, Cornelia M. Van Duijn

University of Oxford
German Research Center for Environmental Health
University of Regensburg
Innsbruck Medical University
deCODE Genetics
Harvard T.H. Chan School of Public Health
Harvard Medical School
Massachusetts General Hospital
Broad Institute of MIT and Harvard
University of Michigan, Ann Arbor
Medical Genetics
King's College London
Wellcome Sanger Institute
Imperial College London
Addenbrooke's Hospital
Boston Children's Hospital and Harvard Medical School
Institute of Legal Informatics and Judicial Systems (IGSiG-CNR)
University of Bristol
Skåne University Hospital
Geriatric Unit
Keck School of Medicine of USC
National Human Genome Research Institute (NHGRI)
National Cancer Institute (Bethesda, Md)
MRC Lifecourse Epidemiology Unit
Glasgow Cardiovascular Research Centre
University of Dundee School of Medicine
Erasmus University Rotterdam
National Institutes of Health

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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
Article number	e1000508
Journal	PLoS Genetics
Volume	5
Issue number	6
DOIs	https://doi.org/10.1371/journal.pgen.1000508
Publication status	Published - Jun 2009

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Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat DistributionFinal published version, 583 KB

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Lindgren, C. M., Heid, I. M., groep, Randall, J. C., Lamina, C., Steinthorsdottir, V., Qi, L., Speliotes, E. K., Thorleifsson, G., Willer, C. J., Herrera, B. M., Jackson, A. U., Lim, N., Scheet, P., Soranzo, N., Amin, N., Aulchenko, Y. S., Chambers, J. C., Drong, A., ... Van Duijn, C. M. (2009). Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genetics, 5(6), Article e1000508. https://doi.org/10.1371/journal.pgen.1000508

@article{52d851b20e8b46e0a35e2bd61e6619d5,

title = "Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution",

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{\texttimes}102 -11) and MSRA (WC, P = 8.9{\texttimes}10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6{\texttimes}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.",

author = "Lindgren, \{Cecilia M.\} and Heid, \{Iris M.\} and groep and Randall, \{Joshua C.\} and Claudia Lamina and Valgerdur Steinthorsdottir and Lu Qi and Speliotes, \{Elizabeth K.\} and Gudmar Thorleifsson and Willer, \{Cristen J.\} and Herrera, \{Blanca M.\} and Jackson, \{Anne U.\} and Noha Lim and Paul Scheet and Nicole Soranzo and Najaf Amin and Aulchenko, \{Yurii S.\} and Chambers, \{John C.\} and Alexander Drong and Luan, \{Jia N.an\} and Lyon, \{Helen N.\} and Fernando Rivadeneira and Serena Sanna and Timpson, \{Nicholas J.\} and Zillikens, \{M. Carola\} and Jing, \{Hua Zhao\} and Peter Almgren and Stefania Bandinelli and Bennett, \{Amanda J.\} and Bergman, \{Richard N.\} and Bonnycastle, \{Lori L.\} and Bumpstead, \{Suzannah J.\} and Chanock, \{Stephen J.\} and Lynn Cherkas and Peter Chines and Lachlan Coin and Cyrus Cooper and Gabriel Crawford and Angela Doering and Anna Dominiczak and Doney, \{Alex S.F.\} and Shah Ebrahim and Paul Elliott and Erdos, \{Michael R.\} and Karol Estrada and Luigi Ferrucci and Albert Hofman and Jacobs, \{Leonie C.\} and Oostra, \{Ben A.\} and Uitterlinden, \{Andr{\'e} G.\} and \{Van Duijn\}, \{Cornelia M.\}",

year = "2009",

month = jun,

doi = "10.1371/journal.pgen.1000508",

language = "English",

volume = "5",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "6",

}

Lindgren, CM, Heid, IM, groep, Randall, JC, Lamina, C, Steinthorsdottir, V, Qi, L, Speliotes, EK, Thorleifsson, G, Willer, CJ, Herrera, BM, Jackson, AU, Lim, N, Scheet, P, Soranzo, N, Amin, N, Aulchenko, YS, Chambers, JC, Drong, A, Luan, JNA, Lyon, HN, Rivadeneira, F, Sanna, S, Timpson, NJ, Zillikens, MC, Jing, HZ, Almgren, P, Bandinelli, S, Bennett, AJ, Bergman, RN, Bonnycastle, LL, Bumpstead, SJ, Chanock, SJ, Cherkas, L, Chines, P, Coin, L, Cooper, C, Crawford, G, Doering, A, Dominiczak, A, Doney, ASF, Ebrahim, S, Elliott, P, Erdos, MR, Estrada, K, Ferrucci, L, Hofman, A, Jacobs, LC, Oostra, BA, Uitterlinden, AG & Van Duijn, CM 2009, 'Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution', PLoS Genetics, vol. 5, no. 6, e1000508. https://doi.org/10.1371/journal.pgen.1000508

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 - groep

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 - Hofman, Albert

AU - Jacobs, Leonie C.

AU - Oostra, Ben A.

AU - Uitterlinden, André G.

AU - Van Duijn, Cornelia M.

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 - https://www.scopus.com/pages/publications/67651236725

U2 - 10.1371/journal.pgen.1000508

DO - 10.1371/journal.pgen.1000508

M3 - Article

C2 - 19557161

AN - SCOPUS:67651236725

SN - 1553-7390

VL - 5

JO - PLoS Genetics

JF - PLoS Genetics

IS - 6

M1 - e1000508

ER -

Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

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