A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape.
Janina S RiedJanina Jeff MAudrey Y ChuJennifer L Bragg-GreshamJenny van DongenJennifer E HuffmanTarunveer S AhluwaliaGemma CadbyNiina EklundJoel ErikssonTõnu EskoMary F FeitosaAnuj GoelMathias GorskiCaroline HaywardNancy L Heard-CostaAnne U JacksonEero JokinenStavroula KanoniKati KristianssonZoltán KutalikJari LahtiJian'an LuanReedik MägiAnubha MahajanMassimo ManginoCarolina Medina-GomezKeri L MondaIlja Maria NolteLouis PérusseInga ProkopenkoLu QiLynda M RoseErika SalviMegan T SmithHarold SniederAlena StančákováYun Ju SungIoanna TachmazidouAlexander TeumerGudmar ThorleifssonPim van der HarstRyan W WalkerSophie R WangSarah H WildSara M WillemsAndrew WongWeihua ZhangEva AlbrechtAlexessander Couto AlvesStephan J L BakkerCristina BarlassinaTraci M BartzJohn P BeilbyClaire BellisRichard N BergmanSven BergmannJohn BlangeroMatthias BlüherEric BoerwinkleLori L BonnycastleStefan R BornsteinMarcel BruinenbergHarry CampbellYii-Der Ida ChenCharleston W K ChiangPeter S ChinesFrancis S CollinsFracensco CuccaL Adrienne CupplesFrancesca D'AvilaEco J C de GeusGeorge DedoussisMaria DimitriouAngela DöringJohan G ErikssonAliki-Eleni FarmakiMartin FarrallTeresa FerreiraKrista FischerNita G ForouhiNele FriedrichAnette Prior GjesingNicola GloriosoMariaelisa GraffHarald GrallertNiels GrarupJürgen GräßlerJagvir GrewalAnders HamstenMarie Neergaard HarderCatharina A HartmanMaija HassinenNicholas HastieAndrew Tym HattersleyAki S HavulinnaMarkku HeliövaaraHans HillegeAlbert HofmanOddgeir HolmenGeorg HomuthJouke-Jan HottengaJennie HuiLise Lotte HusemoenPirro G HysiAaron IsaacsTill IttermannShapour JalilzadehAlan L JamesTorben JørgensenPekka JousilahtiAntti JulaJohanne Marie JustesenAnne E JusticeMika KähönenMaria KaraleftheriKay Tee KhawSirkka M Keinanen-KiukaanniemiLeena KinnunenPaul B KnektHeikki A KoistinenIvana KolcicIshminder K KoonerSeppo KoskinenPeter KovacsTheodosios KyriakouTomi LaitinenClaudia LangenbergAlexandra M LewinPeter LichtnerCecilia M LindgrenJaana LindströmAllan LinnebergRoberto LorbeerMattias LorentzonRobert LubenValeriya LyssenkoSatu MännistöPaolo ManuntaIrene Mateo LeachWendy L McArdleBarbara McknightKaren L MohlkeEvelin MihailovLili MilaniRebecca MillsMay E MontasserAndrew P MorrisGabriele MüllerArthur W MuskNarisu NarisuKen K OngBen A OostraClive OsmondAarno PalotieJames S PankowLavinia PaternosterBrenda W PenninxIrene PichlerMaria G PiliaOzren PolašekPeter P PramstallerOlli T RaitakariTuomo RankinenD C RaoNigel W RaynerRasmus Ribel-MadsenTreva K RiceMarcus RichardsPaul M RidkerFernando RivadeneiraKathy A RyanSerena SannaMark A SarzynskiSalome ScholtensRobert A ScottSylvain SebertLorraine SouthamThomas Hempel SparsøValgerdur SteinthorsdottirKathleen StirrupsRonald P StolkKonstantin StrauchHeather M StringhamMorris A SwertzAmy J SwiftAnke TönjesEmmanouil TsafantakisPeter J van der MostJana V Van Vliet-OstaptchoukLiesbeth VandenputErkki VartiainenCristina VenturiniNiek VerweijJorma S ViikariVeronique VitartMarie-Claude VohlJudith M VonkGérard WaeberElisabeth WidénGonneke WillemsenTom WilsgaardThomas W WinklerAlan F WrightLaura M Yerges-ArmstrongJing Hua ZhaoM Carola ZillikensDorret I BoomsmaClaude BouchardJohn C ChambersDaniel I ChasmanDaniele CusiRon T GansevoortChristian GiegerTorben HansenAndrew A HicksFrank HuKristian HveemMarjo-Riitta JarvelinEero KajantieJaspal S KoonerDiana KuhJohanna KuusistoMarkku LaaksoTimo A LakkaTerho LehtimäkiAndres MetspaluInger NjølstadClaes OhlssonAlbertine J OldehinkelLyle J PalmerOluf PedersenMarkus PerolaAnnette PetersBruce M PsatyHannu PuolijokiRainer RauramaaIgor RudanVeikko SalomaaPeter E H SchwarzAlan R ShudinerJan H SmitThorkild I A SørensenTimothy D SpectorKari StefanssonMichael StumvollAngelo TremblayJaakko TuomilehtoAndré G UitterlindenMatti UusitupaUwe VölkerPeter VollenweiderNicholas J WarehamHugh WatkinsJames F WilsonEleftheria ZegginiGoncalo R AbecasisMichael BoehnkeIngrid B BoreckiPanos DeloukasCornelia M van DuijnCaroline FoxLeif C GroopIris M HeidDavid J HunterRobert C KaplanMark I McCarthyKari E NorthJeffrey R O'ConnellDavid SchlessingerUnnur ThorsteinsdottirDavid P StrachanTimothy FraylingJoel N HirschhornMartina Müller-NurasyidRuth J F LoosPublished in: Nature communications (2016)
Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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