biostudies-literatureKilpelainen TONICHD NIH HHSNIA NIH HHSNCRR NIH HHSNHLBI NIH HHSNNF Center for Basic Metabolic ResearchDanish Diabetes and Endocrine AcademyNIDDK NIH HHSMedical Research CouncilNational Institute for Health Research (NIHR)NHGRI NIH HHSNCI NIH HHSNovo Nordisk FondenBiotechnology and Biological Sciences Research Council376https://www.ebi.ac.uk/biostudies/studies/S-EPMC6342931biostudies-literatureUnknown10(1)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 cholesterNature communicationsMulti-ancestry study of blood lipid levels identifies four loci interacting with physical activity.PMC6342931UM1 CA182910NF-SI-0617-10149T32 DK091317U01 HG007417K01 HL136700U01 DK062370UM1 CA173640P01 CA196569P30 DK056341R01 DK093757MC_UU_12015/1U01 HL120393NF-SI-0611-10170P30 DK020572R01 HL119443R01 HL046380M01 RR000032PhD006-18MC_PC_13046MC_PC_13048NNF17OC0026848K01 HL135405U01 AG009740MC_UU_00007/10BB/F019394/1G0700704BR01 AG055406R01 HL120393U01 HL137162MR/K026992/1HDR-2002MR/L01341X/1R01 DK075787R01 HL118305MR/R023484/1R01 HL113338Kilpeläinen GroupP2C HD050924R35 HL135818R01 DK107786R01 HL142302R01 DK062370P30 DK079626P30 DK020541MR/L01632X/1R01 DK072193R01 HL105756Cupples LAPsaty BMBowden DWKardia SLRUitterlinden AGNavis GManning AVerweij NGabriel KPPazoki RZhao JHCanouil MMosley THde las Fuentes LVan Vliet-Ostaptchouk JVNolte IMEsko Tde Silva HJWeir DRHe JPoveda AHe MRaitakari OTTsai MYRobino ABartz TMLyytikainen LPStrauch KLangefeld CDAmini MWennberg PBoezen HMCade BFisher VScott RAWang YXJakupovic HNorris JMJackson AUConcas MPGiulianini FWaldenberger MZhao WLoos RJFMunroe PBPenninx BWJHWagenknecht LEBrown MRSims MLemaitre RNKooperberg CBSmith AVTaylor KDRidker PMHeng CKvan Dam RMKho MKuusisto JMilaneschi YAschard HLaguzzi FBoehnke MFaul JDYu CVollenweider PPapanicolau GJFox ERAlizadeh BZRose LMWijmenga CZhu XMohlke KLFriedlander YPeters ARotter JIRots MRich SSGasparini PHsu FCTakeuchi FChen XGieger CLi CMagi RFranceschini NSchreiner PJGu CCvan Duijn CMLi XKilpelainen TOde Mutsert RSamani NJLiu CTRobinson JGTajuddin SMLifelines Cohort StudyKelly TNde Faire UFornage MBrumat MLiu JFeitosa MFWinkler TWAlver MLiu YArnett DKStringham HMMetspalu ASnieder HNtalla ILauner LJvan der Ende MYXiang YBFroguel PKuhnel BLeander KProvince MAGuo XRice KGudnason VBielak LFTai ESMorrison ACChasman DIRichard MNwuba CVHarris SEDeary IJEvangelou ELiang JIkram MAMook-Kanamori DOOldehinkel AJSung YJRiaz MMurray ADHayward CRotimi CNRisch NKritchevsky SBEaton CBMusani SKZheng WNelson CPMagnusson PKERedline SConnell JVoortman TSchwander KHarris TBNoordam RWare EBSwertz MSidney SSRauramaa RLaakso MNalls MAYanek LRFranks PWFranke LAmin NDorajoo RKraja ATHorimoto ARVRGraff MRueedi RLohman KKTang HGauderman WJKoh WPPedersen NLWareham NJSmith JAPereira ACVojinovic DDivers JLewis CEYuan JMBoissel MSternfeld BDemirkan APalmer NDBecker DMHunt SCStarr JMWilson GKomulainen PLakka TAde Vries PSBoerwinkle EElliott PWang HGao CWen WChai JFGu DZonderman ABNang EKMarten JMeitinger TWu TWang ZKrieger JEYao JVarga TVFreedman BIPorteous DJHeikkinen SEvans MKManichaikul AO'Connell JPeyser PAAslibekyan STuomilehto JKutalik Zvan der Most PJPolasek ODing JBentley ARWolffenbuttel BHRHorta BLSofer TKato NLehtimaki Tvan der Harst PGhanbari MRudan IHartwig FPShu XORao DCSim XLangenberg CNona SJonas JBCampbell Avan Heemst DChen YINorth KEfalseMulti-ancestry study of blood lipid levels identifies four loci interacting with physical activity.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 cholester2019-01-01T00:00:00Z2019 Jan2026-04-15T13:08:41.193Z2019-03-26T22:41:04ZS-EPMC63429313067069710.1038/s41467-018-08008-w