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; Anuj Goel; Anne U Jackson; Toby Johnson; Marcus E Kleber; Kati Kristiansson; Massimo Mangino; Irene Mateo Leach; ADIPOGen Consortium(Lise Tarnow,member); Lise Tarnow

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, Anuj Goel, Anne U Jackson, Toby Johnson, Marcus E Kleber, Kati Kristiansson, Massimo Mangino, Irene Mateo Leach, ADIPOGen Consortium(Lise Tarnow,member), Lise Tarnow (Medlem af forfattergruppering)

1170 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature
Vol/bind	518
Udgave nummer	7538
Sider (fra-til)	187-96
Antal sider	10
ISSN	0028-0836
DOI	https://doi.org/10.1038/nature14132
Status	Udgivet - 12 feb. 2015
Udgivet eksternt	Ja

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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., ... Tarnow, L. (2015). New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518(7538), 187-96. https://doi.org/10.1038/nature14132

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, Mangino, M, Mateo Leach, I, ADIPOGen Consortium(Lise Tarnow,member) & Tarnow, L 2015, 'New genetic loci link adipose and insulin biology to body fat distribution', Nature, bind 518, nr. 7538, s. 187-96. https://doi.org/10.1038/nature14132

@article{2084eb0439544c9290fd5c1eb5682d54,

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 Anuj Goel and Jackson, {Anne U} and Toby Johnson and Kleber, {Marcus E} and Kati Kristiansson and Massimo Mangino and {Mateo Leach}, Irene and {ADIPOGen Consortium(Lise Tarnow,member)} and Lise Tarnow",

year = "2015",

month = feb,

day = "12",

doi = "10.1038/nature14132",

language = "English",

volume = "518",

pages = "187--96",

journal = "Nature",

issn = "0028-0836",

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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 - Mangino, Massimo

AU - Mateo Leach, Irene

AU - ADIPOGen Consortium(Lise Tarnow,member)

A2 - Tarnow, Lise

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 - Journal 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

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