Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Iris M Heid; Anne U Jackson; Joshua C Randall; Thomas W Winkler; Lu Qi; Valgerdur Steinthorsdottir; Gudmar Thorleifsson; M Carola Zillikens; Elizabeth K Speliotes; Reedik Mägi; Tsegaselassie Workalemahu; Charles C White; Nabila Bouatia-Naji; Tamara B Harris; Sonja I Berndt; Erik Ingelsson; Cristen J Willer; Michael N Weedon; Jian'an Luan; Sailaja Vedantam; Tõnu Esko; Tuomas Oskari Kilpeläinen; Zoltán Kutalik; Shengxu Li; Keri L Monda; Anna L Dixon; Christopher C Holmes; Lee M Kaplan; Liming Liang; Josine L Min; Miriam F Moffatt; Cliona Molony; George Nicholson; Eric E Schadt; Krina T Zondervan; Mary F Feitosa; Teresa Ferreira; Hana Lango Allen; Robert J Weyant; Eleanor Wheeler; Andrew R Wood; Karol Estrada; Michael E Goddard; Guillaume Lettre; Massimo Mangino; Anette P Gjesing; Daniel R Witte; Torben Hansen; Torben Jørgensen; Oluf Pedersen; MAGIC

doi:10.1038/ng.685

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Iris M Heid, Anne U Jackson, Joshua C Randall, Thomas W Winkler, Lu Qi, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, M Carola Zillikens, Elizabeth K Speliotes, Reedik Mägi, Tsegaselassie Workalemahu, Charles C White, Nabila Bouatia-Naji, Tamara B Harris, Sonja I Berndt, Erik Ingelsson, Cristen J Willer, Michael N Weedon, Jian'an Luan, Sailaja VedantamTõnu Esko, Tuomas Oskari Kilpeläinen, Zoltán Kutalik, Shengxu Li, Keri L Monda, Anna L Dixon, Christopher C Holmes, Lee M Kaplan, Liming Liang, Josine L Min, Miriam F Moffatt, Cliona Molony, George Nicholson, Eric E Schadt, Krina T Zondervan, Mary F Feitosa, Teresa Ferreira, Hana Lango Allen, Robert J Weyant, Eleanor Wheeler, Andrew R Wood, Karol Estrada, Michael E Goddard, Guillaume Lettre, Massimo Mangino, Anette P Gjesing, Daniel R Witte, Torben Hansen, Torben Jørgensen, Oluf Pedersen, MAGIC

660 Citations (Scopus)

Abstract

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Original language	English
Journal	Nature Genetics
Volume	42
Issue number	11
Pages (from-to)	949-60
Number of pages	12
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.685
Publication status	Published - 1 Nov 2010

Keywords

Adipose Tissue
Age Factors
Chromosome Mapping
Female
Genome, Human
Genome-Wide Association Study
Humans
Male
Meta-Analysis as Topic
Polymorphism, Single Nucleotide
Sex Characteristics
Waist-Hip Ratio

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Heid, I. M., Jackson, A. U., Randall, J. C., Winkler, T. W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M. C., Speliotes, E. K., Mägi, R., Workalemahu, T., White, C. C., Bouatia-Naji, N., Harris, T. B., Berndt, S. I., Ingelsson, E., Willer, C. J., Weedon, M. N., Luan, J., ... MAGIC (2010). Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nature Genetics, 42(11), 949-60. https://doi.org/10.1038/ng.685

Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L, Steinthorsdottir, V, Thorleifsson, G, Zillikens, MC, Speliotes, EK, Mägi, R, Workalemahu, T, White, CC, Bouatia-Naji, N, Harris, TB, Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, J, Vedantam, S, Esko, T, Oskari Kilpeläinen, T, Kutalik, Z, Li, S, Monda, KL, Dixon, AL, Holmes, CC, Kaplan, LM, Liang, L, Min, JL, Moffatt, MF, Molony, C, Nicholson, G, Schadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Allen, HL, Weyant, RJ, Wheeler, E, Wood, AR, Estrada, K, Goddard, ME, Lettre, G, Mangino, M, Gjesing, AP, Witte, DR, Hansen, T, Jørgensen, T, Pedersen, O & MAGIC 2010, 'Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution', Nature Genetics, vol. 42, no. 11, pp. 949-60. https://doi.org/10.1038/ng.685

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title = "Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution",

abstract = "Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.",

keywords = "Adipose Tissue, Age Factors, Chromosome Mapping, Female, Genome, Human, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Sex Characteristics, Waist-Hip Ratio",

author = "Heid, {Iris M} and Jackson, {Anne U} and Randall, {Joshua C} and Winkler, {Thomas W} and Lu Qi and Valgerdur Steinthorsdottir and Gudmar Thorleifsson and Zillikens, {M Carola} and Speliotes, {Elizabeth K} and Reedik M{\"a}gi and Tsegaselassie Workalemahu and White, {Charles C} and Nabila Bouatia-Naji and Harris, {Tamara B} and Berndt, {Sonja I} and Erik Ingelsson and Willer, {Cristen J} and Weedon, {Michael N} and Jian'an Luan and Sailaja Vedantam and T{\~o}nu Esko and {Oskari Kilpel{\"a}inen}, Tuomas and Zolt{\'a}n Kutalik and Shengxu Li and Monda, {Keri L} and Dixon, {Anna L} and Holmes, {Christopher C} and Kaplan, {Lee M} and Liming Liang and Min, {Josine L} and Moffatt, {Miriam F} and Cliona Molony and George Nicholson and Schadt, {Eric E} and Zondervan, {Krina T} and Feitosa, {Mary F} and Teresa Ferreira and Allen, {Hana Lango} and Weyant, {Robert J} and Eleanor Wheeler and Wood, {Andrew R} and Karol Estrada and Goddard, {Michael E} and Guillaume Lettre and Massimo Mangino and Gjesing, {Anette P} and Witte, {Daniel R} and Torben Hansen and Torben J{\o}rgensen and Oluf Pedersen and MAGIC",

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doi = "10.1038/ng.685",

language = "English",

volume = "42",

pages = "949--60",

journal = "Nature: New biology",

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T1 - Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

AU - Heid, Iris M

AU - Jackson, Anne U

AU - Randall, Joshua C

AU - Winkler, Thomas W

AU - Qi, Lu

AU - Steinthorsdottir, Valgerdur

AU - Thorleifsson, Gudmar

AU - Zillikens, M Carola

AU - Speliotes, Elizabeth K

AU - Mägi, Reedik

AU - Workalemahu, Tsegaselassie

AU - White, Charles C

AU - Bouatia-Naji, Nabila

AU - Harris, Tamara B

AU - Berndt, Sonja I

AU - Ingelsson, Erik

AU - Willer, Cristen J

AU - Weedon, Michael N

AU - Luan, Jian'an

AU - Vedantam, Sailaja

AU - Esko, Tõnu

AU - Oskari Kilpeläinen, Tuomas

AU - Kutalik, Zoltán

AU - Li, Shengxu

AU - Monda, Keri L

AU - Dixon, Anna L

AU - Holmes, Christopher C

AU - Kaplan, Lee M

AU - Liang, Liming

AU - Min, Josine L

AU - Moffatt, Miriam F

AU - Molony, Cliona

AU - Nicholson, George

AU - Schadt, Eric E

AU - Zondervan, Krina T

AU - Feitosa, Mary F

AU - Ferreira, Teresa

AU - Allen, Hana Lango

AU - Weyant, Robert J

AU - Wheeler, Eleanor

AU - Wood, Andrew R

AU - Estrada, Karol

AU - Goddard, Michael E

AU - Lettre, Guillaume

AU - Mangino, Massimo

AU - Gjesing, Anette P

AU - Witte, Daniel R

AU - Hansen, Torben

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - MAGIC

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

AB - Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

KW - Adipose Tissue

KW - Age Factors

KW - Chromosome Mapping

KW - Female

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Meta-Analysis as Topic

KW - Polymorphism, Single Nucleotide

KW - Sex Characteristics

KW - Waist-Hip Ratio

U2 - 10.1038/ng.685

DO - 10.1038/ng.685

M3 - Journal article

C2 - 20935629

SN - 1061-4036

VL - 42

SP - 949

EP - 960

JO - Nature: New biology

JF - Nature: New biology

IS - 11

ER -

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Abstract

Keywords

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