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, Anuj Goel, Anne U Jackson, Toby Johnson, Marcus E Kleber, Kati Kristiansson, Eoin P Brennan, Amy J McKnight, Frank Kee, ADIPOGen Consortium

Research output: Contribution to journalArticle

519 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 languageEnglish
Pages (from-to)187-196
Number of pages10
JournalNature
Volume518
Issue number7538
Early online date11 Feb 2015
DOIs
Publication statusPublished - 12 Feb 2015

Fingerprint

Body Fat Distribution
Genetic Loci
Waist-Hip Ratio
Waist Circumference
Hip
Body Mass Index
Insulin
Adipogenesis
Genome-Wide Association Study
Adiposity
Adipocytes
Sex Characteristics
Insulin Resistance
Meta-Analysis
Adipose Tissue
Fats
Genes

Cite this

Shungin, D., Winkler, T. W., Croteau-Chonka, D. C., Ferreira, T., Locke, A. E., Mägi, R., ... ADIPOGen Consortium (2015). New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518(7538), 187-196. https://doi.org/10.1038/nature14132
Shungin, Dmitry ; Winkler, Thomas W ; Croteau-Chonka, Damien C ; Ferreira, Teresa ; Locke, Adam E ; Mägi, Reedik ; Strawbridge, Rona J ; Pers, Tune H ; Fischer, Krista ; Justice, Anne E ; Workalemahu, Tsegaselassie ; Wu, Joseph M W ; Buchkovich, Martin L ; Heard-Costa, Nancy L ; Roman, Tamara S ; Drong, Alexander W ; Song, Ci ; Gustafsson, Stefan ; Day, Felix R ; Esko, Tonu ; Fall, Tove ; Kutalik, Zoltán ; Luan, Jian'an ; Randall, Joshua C ; Scherag, André ; Vedantam, Sailaja ; Wood, Andrew R ; Chen, Jin ; Fehrmann, Rudolf ; Karjalainen, Juha ; Kahali, Bratati ; Liu, Ching-Ti ; Schmidt, Ellen M ; Absher, Devin ; Amin, Najaf ; Anderson, Denise ; Beekman, Marian ; Bragg-Gresham, Jennifer L ; Buyske, Steven ; Demirkan, Ayse ; Ehret, Georg B ; Feitosa, Mary F ; Goel, Anuj ; Jackson, Anne U ; Johnson, Toby ; Kleber, Marcus E ; Kristiansson, Kati ; Brennan, Eoin P ; McKnight, Amy J ; Kee, Frank ; ADIPOGen Consortium. / New genetic loci link adipose and insulin biology to body fat distribution. In: Nature. 2015 ; Vol. 518, No. 7538. pp. 187-196.
@article{f6a5405e39dd473db00231cace4e52c5,
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.",
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 Anuj Goel and Jackson, {Anne U} and Toby Johnson and Kleber, {Marcus E} and Kati Kristiansson and Brennan, {Eoin P} and McKnight, {Amy J} and Frank Kee and {ADIPOGen Consortium}",
year = "2015",
month = "2",
day = "12",
doi = "10.1038/nature14132",
language = "English",
volume = "518",
pages = "187--196",
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, Goel, A, Jackson, AU, Johnson, T, Kleber, ME, Kristiansson, K, Brennan, EP, McKnight, AJ, Kee, F & ADIPOGen Consortium 2015, 'New genetic loci link adipose and insulin biology to body fat distribution', Nature, vol. 518, no. 7538, pp. 187-196. https://doi.org/10.1038/nature14132

New genetic loci link adipose and insulin biology to body fat distribution. / Shungin, Dmitry; Winkler, Thomas W; Croteau-Chonka, Damien C; Ferreira, Teresa; Locke, Adam E; Mägi, Reedik; Strawbridge, Rona J; Pers, Tune H; Fischer, Krista; Justice, Anne E; Workalemahu, Tsegaselassie; Wu, Joseph M W; Buchkovich, Martin L; Heard-Costa, Nancy L; Roman, Tamara S; Drong, Alexander W; Song, Ci; Gustafsson, Stefan; Day, Felix R; Esko, Tonu; Fall, Tove; Kutalik, Zoltán; Luan, Jian'an; Randall, Joshua C; Scherag, André; Vedantam, Sailaja; Wood, Andrew R; Chen, Jin; Fehrmann, Rudolf; Karjalainen, Juha; Kahali, Bratati; Liu, Ching-Ti; Schmidt, Ellen M; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bragg-Gresham, Jennifer L; Buyske, Steven; Demirkan, Ayse; Ehret, Georg B; Feitosa, Mary F; Goel, Anuj; Jackson, Anne U; Johnson, Toby; Kleber, Marcus E; Kristiansson, Kati; Brennan, Eoin P; McKnight, Amy J; Kee, Frank; ADIPOGen Consortium.

In: Nature, Vol. 518, No. 7538, 12.02.2015, p. 187-196.

Research output: Contribution to journalArticle

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 - Goel, Anuj

AU - Jackson, Anne U

AU - Johnson, Toby

AU - Kleber, Marcus E

AU - Kristiansson, Kati

AU - Brennan, Eoin P

AU - McKnight, Amy J

AU - Kee, Frank

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.

U2 - 10.1038/nature14132

DO - 10.1038/nature14132

M3 - Article

C2 - 25673412

VL - 518

SP - 187

EP - 196

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7538

ER -

Shungin D, Winkler TW, Croteau-Chonka DC, Ferreira T, Locke AE, Mägi R et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature. 2015 Feb 12;518(7538):187-196. https://doi.org/10.1038/nature14132