학술논문

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
Document Type
article
Author
Cecilia M LindgrenIris M HeidJoshua C RandallClaudia LaminaValgerdur SteinthorsdottirLu QiElizabeth K SpeliotesGudmar ThorleifssonCristen J WillerBlanca M HerreraAnne U JacksonNoha LimPaul ScheetNicole SoranzoNajaf AminYurii S AulchenkoJohn C ChambersAlexander DrongJian'an LuanHelen N LyonFernando RivadeneiraSerena SannaNicholas J TimpsonM Carola ZillikensJing Hua ZhaoPeter AlmgrenStefania BandinelliAmanda J BennettRichard N BergmanLori L BonnycastleSuzannah J BumpsteadStephen J ChanockLynn CherkasPeter ChinesLachlan CoinCyrus CooperGabriel CrawfordAngela DoeringAnna DominiczakAlex S F DoneyShah EbrahimPaul ElliottMichael R ErdosKarol EstradaLuigi FerrucciGuido FischerNita G ForouhiChristian GiegerHarald GrallertChristopher J GrovesScott GrundyCandace GuiducciDavid HadleyAnders HamstenAki S HavulinnaAlbert HofmanRolf HolleJohn W HollowayThomas IlligBo IsomaaLeonie C JacobsKaren JamesonPekka JousilahtiFredrik KarpeJohanna KuusistoJaana LaitinenG Mark LathropDebbie A LawlorMassimo ManginoWendy L McArdleThomas MeitingerMario A MorkenAndrew P MorrisPatricia MunroeNarisu NarisuAnna NordströmPeter NordströmBen A OostraColin N A PalmerFelicity PayneJohn F PedenInga ProkopenkoFrida RenströmAimo RuokonenVeikko SalomaaManjinder S SandhuLaura J ScottAngelo ScuteriKaisa SilanderKijoung SongXin YuanHeather M StringhamAmy J SwiftTiinamaija TuomiManuela UdaPeter VollenweiderGerard WaeberChris WallaceG Bragi WaltersMichael N WeedonWellcome Trust Case Control ConsortiumJacqueline C M WittemanCuilin ZhangWeihua ZhangMark J CaulfieldFrancis S CollinsGeorge Davey SmithIan N M DayPaul W FranksAndrew T HattersleyFrank B HuMarjo-Riitta JarvelinAugustine KongJaspal S KoonerMarkku LaaksoEdward LakattaVincent MooserAndrew D MorrisLeena PeltonenNilesh J SamaniTimothy D SpectorDavid P StrachanToshiko TanakaJaakko TuomilehtoAndré G UitterlindenCornelia M van DuijnNicholas J WarehamHugh WatkinsProcardis ConsortiaDawn M WaterworthMichael BoehnkePanos DeloukasLeif GroopDavid J HunterUnnur ThorsteinsdottirDavid SchlessingerH-Erich WichmannTimothy M FraylingGonçalo R AbecasisJoel N HirschhornRuth J F LoosKari StefanssonKaren L MohlkeInês BarrosoMark I McCarthyGiant Consortium
Source
PLoS Genetics, Vol 5, Iss 6, p e1000508 (2009)
Subject
Genetics
QH426-470
Language
English
ISSN
1553-7390
1553-7404
Abstract
To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.