New genetic loci link adipose and insulin biology to body fat distribution

Dmitry Shungin; Thomas W Winkler; Damien C Croteau-Chonka; Teresa Ferreira; Adam E Locke; Reedik Mägi; Rona J Strawbridge; Tune H Pers; Krista Fischer; Anne E Justice; Tsegaselassie Workalemahu; Joseph M W Wu; Martin L Buchkovich; Nancy L Heard-Costa; Tamara S Roman; Alexander W Drong; Ci Song; Stefan Gustafsson; Felix R Day; Tonu Esko; Tove Fall; Zoltán Kutalik; Jian'an Luan; Joshua C Randall; André Scherag; Sailaja Vedantam; Andrew R Wood; Jin Chen; Rudolf Fehrmann; Juha Karjalainen; Bratati Kahali; Ching-Ti Liu; Ellen M Schmidt; Devin Absher; Najaf Amin; Denise Anderson; Marian Beekman; Jennifer L Bragg-Gresham; Steven Buyske; Ayse Demirkan; Georg B Ehret; Mary F Feitosa; Cristina Menni; Alireza Moayyeri; Neil R Robertson; Andrew Wong; James F Wilson; Stefan R Bornstein; John C Chambers; Tim D Spector; ADIPOGen Consortium

doi:10.1038/nature14132

New genetic loci link adipose and insulin biology to body fat distribution

Dmitry Shungin, Thomas W Winkler, Damien C Croteau-Chonka, Teresa Ferreira, Adam E Locke, Reedik Mägi, Rona J Strawbridge, Tune H Pers, Krista Fischer, Anne E Justice, Tsegaselassie Workalemahu, Joseph M W Wu, Martin L Buchkovich, Nancy L Heard-Costa, Tamara S Roman, Alexander W Drong, Ci Song, Stefan Gustafsson, Felix R Day, Tonu EskoTove Fall, Zoltán Kutalik, Jian'an Luan, Joshua C Randall, André Scherag, Sailaja Vedantam, Andrew R Wood, Jin Chen, Rudolf Fehrmann, Juha Karjalainen, Bratati Kahali, Ching-Ti Liu, Ellen M Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Marian Beekman, Jennifer L Bragg-Gresham, Steven Buyske, Ayse Demirkan, Georg B Ehret, Mary F Feitosa, Cristina Menni, Alireza Moayyeri, Neil R Robertson, Andrew Wong, James F Wilson, Stefan R Bornstein, John C Chambers, Tim D Spector, ADIPOGen Consortium

Research output: Contribution to journal › Article › peer-review

1152 Citations (Scopus)

Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Original language	English
Pages (from-to)	187-96
Number of pages	10
Journal	NATURE
Volume	518
Issue number	7538
DOIs	https://doi.org/10.1038/nature14132
Publication status	Published - 12 Feb 2015

Keywords

Adipocytes
Adipogenesis
Adipose Tissue
Age Factors
Body Fat Distribution
Body Mass Index
Continental Population Groups
Epigenesis, Genetic
Europe
Female
Genome, Human
Genome-Wide Association Study
Humans
Insulin
Insulin Resistance
Male
Models, Biological
Neovascularization, Physiologic
Obesity
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Sex Characteristics
Transcription, Genetic
Waist-Hip Ratio

UN SDGs

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

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10.1038/nature14132

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Shungin, D., Winkler, T. W., Croteau-Chonka, D. C., Ferreira, T., Locke, A. E., Mägi, R., Strawbridge, R. J., Pers, T. H., Fischer, K., Justice, A. E., Workalemahu, T., Wu, J. M. W., Buchkovich, M. L., Heard-Costa, N. L., Roman, T. S., Drong, A. W., Song, C., Gustafsson, S., Day, F. R., ... ADIPOGen Consortium (2015). New genetic loci link adipose and insulin biology to body fat distribution. NATURE, 518(7538), 187-96. https://doi.org/10.1038/nature14132

@article{69c95a9347154231aa32358f6b76b46a,

title = "New genetic loci link adipose and insulin biology to body fat distribution",

abstract = "Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.",

keywords = "Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Fat Distribution, Body Mass Index, Continental Population Groups, Epigenesis, Genetic, Europe, Female, Genome, Human, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Male, Models, Biological, Neovascularization, Physiologic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics, Transcription, Genetic, Waist-Hip Ratio",

author = "Dmitry Shungin and Winkler, {Thomas W} and Croteau-Chonka, {Damien C} and Teresa Ferreira and Locke, {Adam E} and Reedik M{\"a}gi and Strawbridge, {Rona J} and Pers, {Tune H} and Krista Fischer and Justice, {Anne E} and Tsegaselassie Workalemahu and Wu, {Joseph M W} and Buchkovich, {Martin L} and Heard-Costa, {Nancy L} and Roman, {Tamara S} and Drong, {Alexander W} and Ci Song and Stefan Gustafsson and Day, {Felix R} and Tonu Esko and Tove Fall and Zolt{\'a}n Kutalik and Jian'an Luan and Randall, {Joshua C} and Andr{\'e} Scherag and Sailaja Vedantam and Wood, {Andrew R} and Jin Chen and Rudolf Fehrmann and Juha Karjalainen and Bratati Kahali and Ching-Ti Liu and Schmidt, {Ellen M} and Devin Absher and Najaf Amin and Denise Anderson and Marian Beekman and Bragg-Gresham, {Jennifer L} and Steven Buyske and Ayse Demirkan and Ehret, {Georg B} and Feitosa, {Mary F} and Cristina Menni and Alireza Moayyeri and Robertson, {Neil R} and Andrew Wong and Wilson, {James F} and Bornstein, {Stefan R} and Chambers, {John C} and Spector, {Tim D} and {ADIPOGen Consortium}",

year = "2015",

month = feb,

day = "12",

doi = "10.1038/nature14132",

language = "English",

volume = "518",

pages = "187--96",

journal = "NATURE",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7538",

}

Shungin, D, Winkler, TW, Croteau-Chonka, DC, Ferreira, T, Locke, AE, Mägi, R, Strawbridge, RJ, Pers, TH, Fischer, K, Justice, AE, Workalemahu, T, Wu, JMW, Buchkovich, ML, Heard-Costa, NL, Roman, TS, Drong, AW, Song, C, Gustafsson, S, Day, FR, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, JC, Scherag, A, Vedantam, S, Wood, AR, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C-T, Schmidt, EM, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg-Gresham, JL, Buyske, S, Demirkan, A, Ehret, GB, Feitosa, MF, Menni, C , Moayyeri, A , Robertson, NR , Wong, A , Wilson, JF , Bornstein, SR , Chambers, JC , Spector, TD & ADIPOGen Consortium 2015, 'New genetic loci link adipose and insulin biology to body fat distribution', NATURE, vol. 518, no. 7538, pp. 187-96. https://doi.org/10.1038/nature14132

TY - JOUR

T1 - New genetic loci link adipose and insulin biology to body fat distribution

AU - Shungin, Dmitry

AU - Winkler, Thomas W

AU - Croteau-Chonka, Damien C

AU - Ferreira, Teresa

AU - Locke, Adam E

AU - Mägi, Reedik

AU - Strawbridge, Rona J

AU - Pers, Tune H

AU - Fischer, Krista

AU - Justice, Anne E

AU - Workalemahu, Tsegaselassie

AU - Wu, Joseph M W

AU - Buchkovich, Martin L

AU - Heard-Costa, Nancy L

AU - Roman, Tamara S

AU - Drong, Alexander W

AU - Song, Ci

AU - Gustafsson, Stefan

AU - Day, Felix R

AU - Esko, Tonu

AU - Fall, Tove

AU - Kutalik, Zoltán

AU - Luan, Jian'an

AU - Randall, Joshua C

AU - Scherag, André

AU - Vedantam, Sailaja

AU - Wood, Andrew R

AU - Chen, Jin

AU - Fehrmann, Rudolf

AU - Karjalainen, Juha

AU - Kahali, Bratati

AU - Liu, Ching-Ti

AU - Schmidt, Ellen M

AU - Absher, Devin

AU - Amin, Najaf

AU - Anderson, Denise

AU - Beekman, Marian

AU - Bragg-Gresham, Jennifer L

AU - Buyske, Steven

AU - Demirkan, Ayse

AU - Ehret, Georg B

AU - Feitosa, Mary F

AU - Menni, Cristina

AU - Moayyeri, Alireza

AU - Robertson, Neil R

AU - Wong, Andrew

AU - Wilson, James F

AU - Bornstein, Stefan R

AU - Chambers, John C

AU - Spector, Tim D

AU - ADIPOGen Consortium

PY - 2015/2/12

Y1 - 2015/2/12

N2 - Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

AB - Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

KW - Adipocytes

KW - Adipogenesis

KW - Adipose Tissue

KW - Age Factors

KW - Body Fat Distribution

KW - Body Mass Index

KW - Continental Population Groups

KW - Epigenesis, Genetic

KW - Europe

KW - Female

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Male

KW - Models, Biological

KW - Neovascularization, Physiologic

KW - Obesity

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Sex Characteristics

KW - Transcription, Genetic

KW - Waist-Hip Ratio

U2 - 10.1038/nature14132

DO - 10.1038/nature14132

M3 - Article

C2 - 25673412

SN - 0028-0836

VL - 518

SP - 187

EP - 196

JO - NATURE

JF - NATURE

IS - 7538

ER -

New genetic loci link adipose and insulin biology to body fat distribution

Abstract

Keywords

UN SDGs

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