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

Dmitry Shungin; Jin Chen; Thomas W Winkler; Denise Anderson; Steven Buyske; 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; Stefan Gustafsson; Felix R Day; Alexander W Drong; Ci Song; Tonu Esko; Tove Fall; Zoltán Kutalik; Jian'An Luan; Joshua C Randall; André Scherag; Sailaja Vedantam; Andrew R Wood; Rudolf Fehrmann; Juha Karjalainen; Bratati Kahali; Ching-Ti Liu; Ellen M Schmidt; Devin Absher; Najaf Amin; Marian Beekman; Jennifer L Bragg-Gresham; 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; Carolina Medina-Gomez; Cameron D Palmer; Dorota Pasko; Sonali Pechlivanis; Marjolein J Peters; Inga Prokopenko; Alena Stančáková; Yun Ju Sung; Toshiko Tanaka; Alexander Teumer; Jana V Van Vliet-Ostaptchouk; Loïc Yengo; Weihua Zhang; Eva Albrecht; Johan Ärnlöv; Gillian M Arscott; Stefania Bandinelli; Amy Barrett; Claire Bellis; Amanda J Bennett; Christian Berne; Matthias Blüher; Stefan Böhringer; Fabrice Bonnet; Yvonne Böttcher; Marcel Bruinenberg; Delia B Carba; Ida H Caspersen; Robert Clarke; E Warwick Daw; Joris Deelen; Ewa Deelman; Graciela Delgado; Alex S F Doney; Niina Eklund; Michael R Erdos; Karol Estrada; Elodie Eury; Nele Friedrich; Melissa E Garcia; Vilmantas Giedraitis; Bruna Gigante; Alan S Go; Alain Golay; Harald Grallert; Tanja B Grammer; Jürgen Gräßler; Jagvir Grewal; Christopher J Groves; Toomas Haller; Goran Hallmans; PAGE Consortium

doi:10.1038/nature14132

Back

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

Journal article

Open access

Peer reviewed

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

Dmitry Shungin, Jin Chen, Thomas W Winkler, Denise Anderson, Steven Buyske, Damien C Croteau-Chonka, Teresa Ferreira, Adam E Locke, Reedik Mägi, Rona J Strawbridge, …

Nature, Vol.518(7538), pp.187-196

02/12/2015

DOI: https://doi.org/10.1038/nature14132

PMCID: PMC4338562

PMID: 25673412

Abstract

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

Life Sciences

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.

Files and links (1)

url

https://doi.org/10.1038/nature14132View

Version of Record (VoR) Open

Metrics

8 Record Views

1078 Times Cited - Web of Science

See more details

Details

Title: New genetic loci link adipose and insulin biology to body fat distribution
Creators: Dmitry Shungin - Department of Clinical Sciences
Jin Chen
Thomas W Winkler
Denise Anderson - Space Sciences Laboratory [Berkeley]
Steven Buyske
Damien C Croteau-Chonka
Teresa Ferreira - Signalisation et Transports Ioniques Membranaires
Adam E Locke
Reedik Mägi
Rona J Strawbridge - Department of Medical Sciences
Tune H Pers - Center for Biological Sequence Analysis [Lyngby]
Krista Fischer
Anne E Justice
Tsegaselassie Workalemahu
Joseph M W Wu - Laboratory of Image Science and Technology [Nanjing]
Martin L Buchkovich
Nancy L Heard-Costa
Tamara S Roman
Stefan Gustafsson - Limnology
Felix R Day
Alexander W Drong
Ci Song
Tonu Esko - Estonian Genome and Medicine
Tove Fall - Department of Medical Epidemiology and Biostatistics
Zoltán Kutalik - Department of Medical Genetics
Jian'An Luan
Joshua C Randall
André Scherag - Institute of Medical Informatics, Biometry and Epidemiology
Sailaja Vedantam
Andrew R Wood
Rudolf Fehrmann
Juha Karjalainen
Bratati Kahali
Ching-Ti Liu
Ellen M Schmidt - Centre d'Immunologie de Marseille - Luminy
Devin Absher
Najaf Amin - Genetic Epidemiology Unit
Marian Beekman
Jennifer L Bragg-Gresham - Department of Biostatistics and Center for Statistical Genetics
Ayse Demirkan - Genetic Epidemiology Unit
Georg B Ehret
Mary F Feitosa - Division of Statistical Genomics
Anuj Goel
Anne U Jackson
Toby Johnson
Marcus E Kleber
Kati Kristiansson
Massimo Mangino - King‘s College London
Irene Mateo Leach
Carolina Medina-Gomez
Cameron D Palmer
Dorota Pasko
Sonali Pechlivanis
Marjolein J Peters
Inga Prokopenko
Alena Stančáková - Department of Medicine
Yun Ju Sung
Toshiko Tanaka
Alexander Teumer - King‘s College London
Jana V Van Vliet-Ostaptchouk - Molecular Genetics Section
Loïc Yengo - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Weihua Zhang
Eva Albrecht
Johan Ärnlöv
Gillian M Arscott
Stefania Bandinelli - Geriatric Rehabilitation Unit
Amy Barrett - Department of Pharmacy Sciences
Claire Bellis
Amanda J Bennett
Christian Berne
Matthias Blüher - Medical Department III
Stefan Böhringer
Fabrice Bonnet - Foie, métabolismes et cancer
Yvonne Böttcher
Marcel Bruinenberg
Delia B Carba
Ida H Caspersen
Robert Clarke
E Warwick Daw
Joris Deelen
Ewa Deelman
Graciela Delgado
Alex S F Doney
Niina Eklund
Michael R Erdos
Karol Estrada - Department of Epidemiology
Elodie Eury
Nele Friedrich
Melissa E Garcia
Vilmantas Giedraitis
Bruna Gigante
Alan S Go
Alain Golay
Harald Grallert - Institute of Epidemiology [Neuherberg]
Tanja B Grammer
Jürgen Gräßler
Jagvir Grewal
Christopher J Groves
Toomas Haller
Goran Hallmans - Department of Public Health and Clinical Medicine
PAGE Consortium
Publication Details: Nature, Vol.518(7538), pp.187-196
Date published: 02/12/2015
Publisher: Nature Publishing Group
Academic Unit: Statistics (SAS)
Language: English
Resource Type: Journal article
Identifiers: 991031665791604646