| | |
Summary: Nature GeNetics VOLUME 42 | NUMBER 11 | NOVEMBER 2010 949
Waist-hipratio(WHR)isameasureofbodyfatdistributionandapredictorofmetabolicconsequencesindependentofoverall
adiposity.WHRisheritable,butfewgeneticvariantsinfluencingthistraithavebeenidentified.Weconductedameta-analysis
of32genome-wideassociationstudiesforWHRadjustedforbodymassindex(comprisingupto77,167participants),following
up16lociinanadditional29studies(comprisingupto113,636subjects).Weidentified13newlociinornearRSPO3,VEGFA,
TBX15-WARS2,NFE2L3,GRB14,DNM3-PIGC,ITPR2-SSPN,LY86,HOXC13,ADAMTS9,ZNRF3-KREMEN1,NISCH-STAB1
andCPEB4(P=1.9×10-9toP=1.8×10-40)andtheknownsignalatLYPLAL1.Sevenoftheselociexhibitedmarkedsexual
dimorphism,allwithastrongereffectonWHRinwomenthanmen(Pforsexdifference=1.9×10-3toP=1.2×10-13).
Thesefindingsprovideevidenceformultiplelocithatmodulatebodyfatdistributionindependentofoveralladiposityandreveal
stronggene-by-sexinteractions.
discovery stage, up to 2,850,269 imputed and genotyped SNPs
wereexaminedin32GWAScomprisingupto77,167participants
informativeforanthropometricmeasuresofbodyfatdistribution.
We performed a fixed-effects meta-analysis of WHR, employing
study-specificlinearregressionadjustedforBMIandage,stratified
bygender,andusinganadditivegeneticmodel.Aftergenomiccontrol
adjustmentpereachindividualstudyandinthemeta-analysis,these
analysesrevealedasubstantialexcessoflowPvalues(Fig. 1a,b).
WeselectedSNPsrepresentingthetop16independent(definedas
beinglocated>1Mbapart)regionsofassociation(discoveryP<1.4×
|
