biostudies-literatureNoordam RIntramural NIH HHSNHLBI NIH HHSNational Institute for Health Research (NIHR)NCI NIH HHS120603https://www.ebi.ac.uk/biostudies/studies/S-EPMC12757440biostudies-literatureUnknown412<h4>Background and aims</h4>Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.<h4>Methods</h4>We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were definedAtherosclerosisGenome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.PMC12757440R21 HL165324NIHR202330R01 HL156991P01 CA196569R01 HL118305R01 HL153814Z01 HG200362Psaty BMProvince MALefevre CVolzke HGuo XMcCormick JBKawaguchi TChen HHShen BMorrison ACZhang RMenni Cvan Dijk KWMatsuda FHarris SEFaquih TKarvonen-Gutierrez CAIkram MAGrabe HJRiha RLWesterman KEPacheco NLHui QMiller CLNolte IMEdwards TLuik AIHe JAnsari MAYTsai MYBelow JEMorrison JLDo ABartz TMGharib SARedline SHixson JCox SRSchwander KNoordam RCade BRauramaa RNorris JMLee SKelly TRuss TCKraja ATNagarajan PMeigs JBZhao WGraff MMunroe PBGauderman WJTang JWagenknecht LEBrown MRde Las Fuentes LTriatin RDimitrov LSmith JAVojinovic DHoughton SCTaylor KDPenninx BWBazzano LFisher-Hoch SPPalmer NDO'Connel JRMilaneschi YAschard HHood MMHuang ZFox ERHingorani AKomulainen PZhu XZhu WPolikowsky HGLakka TAde Vries PSManning AKRotter JIHo YLRao VBoerwinkle EYoung KLRich SSWang HZonderman ABSun QIda Chen YDChen ZMillion Veteran ProgramRuiz-Narvaez EAEvans MSpector TDChen WWang WWang YYao JLi CMagi RRaffield LMFranceschini NXia RChen HDe Anda-Duran IAnugu PHeikkinen SKilpelainen TOLawlor DALiu CTAssimes TLAttia JLifelines Cohort StudyPeyser PAYang QLin HJFornage MGiri Avan der Most PJTeder-Laving MWilson PWCharles Gu CFeitosa MFJaquish CEWinkler TWBentley ARHolliday ETabara YSitlani CMCho KSun YVSofer TMangino MWeiss SNauck MGhanbari MHarlow SDRao DCPetty LESnieder HKals MBallantyne Cvan Heemst DMa JBaker LDGaziano JMLinchangco GVHanfei XNorth KEfalseGenome-wide gene-sleep interaction study identifies novel lipid loci in 732,564 participants.<h4>Background and aims</h4>Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.<h4>Methods</h4>We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined2026-01-01T00:00:00Z2026 Jan2026-06-06T10:39:51.709Z2026-05-29T03:12:39.219ZS-EPMC127574404132569710.1016/j.atherosclerosis.2025.120603