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

Cecilia M. Lindgren; Iris M. Heid; 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; Jian'an Luan; Helen N. Lyon; Fernando Rivadeneira; Serena Sanna; Nicholas J. Timpson; M. Carola Zillikens; Jing Hua Zhao; 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; Guido Fischer; Nita G. Forouhi; Colin N. A. Palmer; George Davey Smith; Andrew D. Morris; Wellcome Trust Case Control Cons, GIANT Consortium, Hugh Watkins PROCARDIS Consortia

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, 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, Jian'an Luan, Helen N. LyonFernando Rivadeneira, Serena Sanna, Nicholas J. Timpson, M. Carola Zillikens, Jing Hua Zhao, 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, Guido Fischer, Nita G. Forouhi, Colin N. A. Palmer, George Davey Smith, Andrew D. Morris, Wellcome Trust Case Control Cons, GIANT Consortium, Hugh Watkins PROCARDIS Consortia

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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 = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-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
Pages (from-to)	-
Number of pages	13
Journal	PLoS Genetics
Volume	5
Issue number	6
DOIs	https://doi.org/10.1371/journal.pgen.1000508
Publication status	Published - Jun 2009

Keywords

FTO GENE
WAIST CIRCUMFERENCE
ADULT OBESITY
ENVIRONMENTAL-CONDITIONS
INSULIN-RESISTANCE
SEQUENCE VARIANTS
COMMON VARIANTS
EXPRESSION
IMPUTATION
HEIGHT

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Lindgren, C. M., Heid, I. M., 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., Luan, J., ... Wellcome Trust Case Control Cons, GIANT Consortium, Hugh Watkins PROCARDIS Consortia (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

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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 = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-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.",

keywords = "FTO GENE, WAIST CIRCUMFERENCE, ADULT OBESITY, ENVIRONMENTAL-CONDITIONS, INSULIN-RESISTANCE, SEQUENCE VARIANTS, COMMON VARIANTS, EXPRESSION, IMPUTATION, HEIGHT",

author = "Lindgren, {Cecilia M.} and Heid, {Iris M.} 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 Jian'an Luan and Lyon, {Helen N.} and Fernando Rivadeneira and Serena Sanna and Timpson, {Nicholas J.} and Zillikens, {M. Carola} and Zhao, {Jing Hua} 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 Guido Fischer and Forouhi, {Nita G.} and Palmer, {Colin N. A.} and Smith, {George Davey} and Morris, {Andrew D.} and {Wellcome Trust Case Control Cons, GIANT Consortium, Hugh Watkins PROCARDIS Consortia}",

year = "2009",

month = jun,

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

language = "English",

volume = "5",

pages = "--",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "6",

}

Lindgren, CM, Heid, IM, 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, J, Lyon, HN, Rivadeneira, F, Sanna, S, Timpson, NJ, Zillikens, MC, Zhao, JH, 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, Fischer, G, Forouhi, NG, Palmer, CNA, Smith, GD, Morris, AD & Wellcome Trust Case Control Cons, GIANT Consortium, Hugh Watkins PROCARDIS Consortia 2009, 'Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution', PLoS Genetics, vol. 5, no. 6, e1000508, pp. -. 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 - 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, Jian'an

AU - Lyon, Helen N.

AU - Rivadeneira, Fernando

AU - Sanna, Serena

AU - Timpson, Nicholas J.

AU - Zillikens, M. Carola

AU - Zhao, Jing Hua

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 - Palmer, Colin N. A.

AU - Smith, George Davey

AU - Morris, Andrew D.

AU - Wellcome Trust Case Control Cons, GIANT Consortium, Hugh Watkins PROCARDIS Consortia

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 = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-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 = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-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.

KW - FTO GENE

KW - WAIST CIRCUMFERENCE

KW - ADULT OBESITY

KW - ENVIRONMENTAL-CONDITIONS

KW - INSULIN-RESISTANCE

KW - SEQUENCE VARIANTS

KW - COMMON VARIANTS

KW - EXPRESSION

KW - IMPUTATION

KW - HEIGHT

U2 - 10.1371/journal.pgen.1000508

DO - 10.1371/journal.pgen.1000508

M3 - Article

C2 - 19557161

SN - 1553-7390

VL - 5

SP - -

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

Abstract

Keywords

UN SDGs

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