New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.

Nat Commun
Authors
Yingchang Lu
Felix Day
Stefan Gustafsson
Martin Buchkovich
Jianbo Na
Veronique Bataille
Diana Cousminer
Zari Dastani
Alexander Drong
Tõnu Esko
David Evans
Mario Falchi
Mary Feitosa
Teresa Ferreira
Åsa Hedman
Robin Haring
Pirro Hysi
Mark Iles
Anne Justice
Stavroula Kanoni
Vasiliki Lagou
Rui Li
Xin Li
Adam Locke
Chen Lu
Reedik Mägi
John Perry
Tune Pers
Qibin Qi
Marianna Sanna
Ellen Schmidt
William Scott
Dmitry Shungin
Alexander Teumer
Anna Vinkhuyzen
Ryan Walker
Harm-Jan Westra
Mingfeng Zhang
Weihua Zhang
Jing Zhao
Zhihong Zhu
Uzma Afzal
Tarunveer Ahluwalia
Stephan Bakker
Claire Bellis
Amelie Bonnefond
Katja Borodulin
Aron Buchman
Tommy Cederholm
Audrey Choh
Hyung Choi
Joanne Curran
Lisette de Groot
Philip De Jager
Rosalie Dhonukshe-Rutten
Anke Enneman
Elodie Eury
Daniel Evans
Tom Forsén
Nele Friedrich
Frédéric Fumeron
Melissa Garcia
Simone Gärtner
Bok-Ghee Han
Aki Havulinna
Caroline Hayward
Dena Hernandez
Hans Hillege
Till Ittermann
Jack Kent
Ivana Kolcic
Tiina Laatikainen
Jari Lahti
Irene Leach
Christine Lee
Jong-Young Lee
Tian Liu
Youfang Liu
Stéphane Lobbens
Marie Loh
Leo-Pekka Lyytikäinen
Carolina Medina-Gomez
Karl Michaëlsson
Mike Nalls
Carrie Nielson
Laticia Oozageer
Laura Pascoe
Lavinia Paternoster
Ozren Polasek
Samuli Ripatti
Mark Sarzynski
Chan Shin
Nina Narančić
Dominik Spira
Priya Srikanth
Elisabeth Steinhagen-Thiessen
Yun Sung
Karin Swart
Leena Taittonen
Toshiko Tanaka
Emmi Tikkanen
Nathalie van der Velde
Natasja van Schoor
Niek Verweij
Alan Wright
Lei Yu
Joseph Zmuda
Niina Eklund
Terrence Forrester
Niels Grarup
Anne Jackson
Kati Kristiansson
Teemu Kuulasmaa
Johanna Kuusisto
Peter Lichtner
Jian'an Luan
Anubha Mahajan
Satu Männistö
Cameron Palmer
Janina Ried
Robert Scott
Alena Stančáková
Peter Wagner
Ayse Demirkan
Angela Döring
Vilmundur Gudnason
Douglas Kiel
Brigitte Kühnel
Massimo Mangino
Barbara McKnight
Cristina Menni
Jeffrey O'Connell
Ben Oostra
Alan Shuldiner
Kijoung Song
Liesbeth Vandenput
Cornelia van Duijn
Peter Vollenweider
Charles White
Michael Boehnke
Yvonne Boettcher
Richard Cooper
Nita Forouhi
Christian Gieger
Harald Grallert
Aroon Hingorani
Torben Jørgensen
Pekka Jousilahti
Mika Kivimaki
Meena Kumari
Markku Laakso
Claudia Langenberg
Allan Linneberg
Amy Luke
Colin McKenzie
Aarno Palotie
Oluf Pedersen
Annette Peters
Konstantin Strauch
Bamidele Tayo
Nicholas Wareham
David Bennett
Lars Bertram
John Blangero
Matthias Blüher
Claude Bouchard
Harry Campbell
Nam Cho
Steven Cummings
Stefan Czerwinski
Ilja Demuth
Rahel Eckardt
Johan Eriksson
Luigi Ferrucci
Oscar Franco
Philippe Froguel
Ron Gansevoort
Torben Hansen
Tamara Harris
Nicholas Hastie
Markku Heliövaara
Albert Hofman
Joanne Jordan
Antti Jula
Mika Kähönen
Eero Kajantie
Paul Knekt
Seppo Koskinen
Peter Kovacs
Terho Lehtimäki
Lars Lind
Yongmei Liu
Eric Orwoll
Clive Osmond
Markus Perola
Louis Pérusse
Olli Raitakari
Tuomo Rankinen
D Rao
Treva Rice
Fernando Rivadeneira
Igor Rudan
Veikko Salomaa
Thorkild Sørensen
Michael Stumvoll
Anke Tönjes
Bradford Towne
Gregory Tranah
Angelo Tremblay
André Uitterlinden
Pim van der Harst
Erkki Vartiainen
Jorma Viikari
Veronique Vitart
Marie-Claude Vohl
Henry Völzke
Mark Walker
Henri Wallaschofski
Sarah Wild
James Wilson
Loic Yengo
D Timothy Bishop
Ingrid Borecki
John Chambers
L Adrienne Cupples
Abbas Dehghan
Panos Deloukas
Ghazaleh Fatemifar
Caroline Fox
Terrence Furey
Lude Franke
Jiali Han
David Hunter
Juha Karjalainen
Fredrik Karpe
Robert Kaplan
Jaspal Kooner
Mark McCarthy
Joanne Murabito
Andrew Morris
Julia Bishop
Kari North
Claes Ohlsson
Ken Ong
Inga Prokopenko
J Brent Richards
Eric Schadt
Tim Spector
Elisabeth Widén
Cristen Willer
Jian Yang
Erik Ingelsson
Karen Mohlke
Joel Hirschhorn
John Pospisilik
M Carola Zillikens
Cecilia Lindgren
Tuomas Kilpeläinen
Ruth Loos
Keywords
Animals
Humans
Gene Expression Regulation
Genetic Predisposition to Disease
Genome-Wide Association Study
Quantitative Trait Loci
Drosophila melanogaster
Gene Knockdown Techniques
Heart Diseases
Adiposity
Abstract

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Year of Publication
2016
Journal
Nat Commun
Volume
7
Pages
10495
Date Published
2016 Feb 01
ISSN
2041-1723
URL
DOI
10.1038/ncomms10495
PubMed ID
26833246
PubMed Central ID
PMC4740398
Links
Grant list
British Heart Foundation / United Kingdom
MC_UP_A100_1003 / Medical Research Council / United Kingdom
R01 DK106236 / DK / NIDDK NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
Medical Research Council / United Kingdom
P30 DK079637 / DK / NIDDK NIH HHS / United States
Biotechnology and Biological Sciences Research Council / United Kingdom
MR/J012165/1 / Medical Research Council / United Kingdom
Department of Health / United Kingdom
R01 DK075787 / DK / NIDDK NIH HHS / United States
MC_UU_12015/1 / Medical Research Council / United Kingdom
MC_U106179471 / Medical Research Council / United Kingdom
K01 HL129892 / HL / NHLBI NIH HHS / United States
MC_UU_12015/2 / Medical Research Council / United Kingdom
MR/J010642/1 / Medical Research Council / United Kingdom
Canadian Institutes of Health Research / Canada
Cancer Research UK / United Kingdom
MC_U106179472 / Medical Research Council / United Kingdom
IK2 CX000729 / CX / CSRD VA / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
MC_UU_12013/4 / Medical Research Council / United Kingdom
MC_PC_U127561128 / Medical Research Council / United Kingdom
Arthritis Research UK / United Kingdom
R01 DK089256 / DK / NIDDK NIH HHS / United States
K01 AR062655 / AR / NIAMS NIH HHS / United States
MR/K006584/1 / Medical Research Council / United Kingdom
MR/K013351/1 / Medical Research Council / United Kingdom
281641 / European Research Council / International
P30 DK020572 / DK / NIDDK NIH HHS / United States
MC_UU_12015/5 / Medical Research Council / United Kingdom
Chief Scientist Office / United Kingdom
MC_UU_12011/4 / Medical Research Council / United Kingdom
R01 HL117078 / HL / NHLBI NIH HHS / United States
10589 / Cancer Research UK / United Kingdom
Wellcome Trust / United Kingdom

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