Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.
Tuomas O KilpeläinenAmy R BentleyRaymond NoordamYun Ju SungKaren SchwanderThomas W WinklerHermina JakupovićDaniel I ChasmanAlisa K ManningIoanna NtallaHugues AschardMichael R BrownLisa de Las FuentesNora FranceschiniXiuqing GuoDina VojinovicStella AslibekyanMary F FeitosaMinjung KhoSolomon K MusaniMelissa A RichardHeming WangZhe WangTraci M BartzLawrence F BielakArchie CampbellRajkumar DorajooVirginia FisherFernando P HartwigAndrea R V R HorimotoChangwei LiKurt K LohmanJonathan MartenXueling SimAlbert V SmithSalman M TajuddinMaris AlverMarzyeh AminiMathilde BoisselJin Fang ChaiXu ChenJasmin DiversEvangelos EvangelouChuan GaoMariaelisa GraffSarah E HarrisMeian HeFang-Chi HsuAnne U JacksonJing Hua ZhaoAldi T KrajaBrigitte KühnelFederica LaguzziLeo-Pekka LyytikäinenIlja M NolteRainer RauramaaMuhammad RiazAntonietta RobinoRico RueediHeather M StringhamFumihiko TakeuchiPeter J van der MostTibor V VargaNiek VerweijErin B WareWanqing WenXiaoyin LiLisa R YanekNajaf AminDonna K ArnettEric BoerwinkleMarco BrumatBrian CadeMickaël CanouilYii-Der Ida ChenMaria Pina ConcasJohn ConnellRenée de MutsertH Janaka de SilvaPaul S de VriesAyşe DemirkanJingzhong DingCharles B EatonJessica D FaulYechiel FriedlanderKelley P GabrielMohsen GhanbariFranco GiulianiniChi Charles GuDongfeng GuTamara B HarrisJiang HeSami HeikkinenChew-Kiat HengSteven C HuntM Arfan IkramJost B JonasWoon-Puay KohPirjo KomulainenJose E KriegerStephen B KritchevskyZoltán KutalikJohanna KuusistoCarl D LangefeldClaudia LangenbergLenore J LaunerKarin LeanderRozenn N LemaitreCora E LewisJingjing Liangnull nullJianjun LiuReedik MägiAni ManichaikulThomas MeitingerAndres MetspaluYuri MilaneschiKaren L MohlkeThomas H MosleyAlison D MurrayMike A NallsEi-Ei Khaing NangChristopher P NelsonSotoodehnia NonaJill M NorrisChiamaka Vivian NwubaJeff O'ConnellNicholette D PalmerGeorge J PapanicolauRaha PazokiNancy L PedersenAnnette PetersPatricia A PeyserOzren PolasekDavid J PorteousAlaitz PovedaOlli T RaitakariStephen S RichNeil RischJennifer G RobinsonLynda M RoseIgor RudanPamela J SchreinerRobert A ScottStephen S SidneyMario SimsJennifer A SmithHarold SniederTamar SoferJohn M StarrBarbara SternfeldKonstantin StrauchHua TangKent D TaylorMichael Y TsaiJaakko TuomilehtoAndré G UitterlindenM Yldau van der EndeDiana van HeemstTrudy VoortmanMelanie WaldenbergerPatrik WennbergGregory WilsonYong-Bing XiangJie YaoCaizheng YuJian-Min YuanWei ZhaoAlan B ZondermanDiane M BeckerMichael BoehnkeDonald W BowdenUlf de FaireIan J DearyPaul ElliottTõnu EskoBarry I FreedmanPhilippe FroguelPaolo GaspariniChristian GiegerNorihiro KatoMarkku LaaksoTimo A LakkaTerho LehtimäkiPatrik K E MagnussonAlbertine J OldehinkelBrenda W J H PenninxNilesh J SamaniXiao-Ou ShuPim van der HarstJana V Van Vliet-OstaptchoukPeter VollenweiderLynne E WagenknechtYa X WangNicholas J WarehamDavid R WeirTangchun WuWei ZhengXiaofeng ZhuMichele K EvansPaul W FranksVilmundur GudnasonCaroline HaywardBernardo L HortaTanika N KellyYongmei LiuKari E NorthAlexandre C PereiraPaul M RidkerE Shyong TaiRob M van DamErvin R FoxSharon L R KardiaChing-Ti LiuDennis O Mook-KanamoriMichael A ProvinceSusan RedlineCornelia M van DuijnJerome I RotterCharles B KooperbergW James GaudermanBruce M PsatyKenneth M RicePatricia B MunroeMyriam FornageL Adrienne CupplesCharles N RotimiAlanna C MorrisonDabeeru C RaoRuth J F LoosPublished in: Nature communications (2019)
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.