Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.
Raymond NoordamMaxime M BosHeming WangThomas W WinklerAmy R BentleyTuomas O KilpeläinenPaul S de VriesYun Ju SungKaren SchwanderBrian E CadeAlisa K ManningHugues AschardMichael R BrownHan ChenNora FranceschiniSolomon K MusaniMelissa A RichardDina VojinovicStella AslibekyanTraci M BartzLisa de Las FuentesMary F FeitosaAndrea R HorimotoMarjan IlkovMinjung KhoAldi KrajaChangwei LiElise LimYongmei LiuDennis O Mook-KanamoriTuomo RankinenSalman M TajuddinAshley van der SpekZhe WangJonathan MartenVincent LavilleMaris AlverEvangelos EvangelouMaria E GraffMeian HeBrigitte KühnelLeo-Pekka LyytikainenPedro-Manuel Marques-VidalIlja Maria NolteNicholette D D AllredRainer RauramaaXiao-Ou ShuHarold SniederStefan WeissWanqing WenLisa R YanekAdolfo CorreaChristie BallantyneLarry BielakNienke R BiermaszEric BoerwinkleNiki L DimouGudny EiriksdottirChuan GaoSina A GharibDaniel J GottliebJosé Haba-RubioTamara B HarrisSami HeikkinenRaphaël HeinzerJames E HixsonGeorg HomuthMohammad Arfan IkramPirjo KomulainenJose Eduardo KriegerJiwon LeeJingmin LiuKurt K LohmanAnnemarie I LuikReedik MägiLisa Warsinger MartinThomas MeitingerAndres MetspaluYuri MilaneschiMike A NallsJeff O'ConnellAnnette PetersPatricia PeyserOlli T RaitakariAlex P ReinerPatrick C N RensenTreva K RiceStephen S RichTill RoennebergJerome I RotterPamela J SchreinerJames ShikanyStephen S SidneyMario SimsColleen M SitlaniTamar SoferKonstantin StrauchMorris A SwertzKent D TaylorAndre G UitterlindenCornelia M van DuijnHenry VölzkeMelanie WaldenbergerRobert B WallanceKo Willems van DijkCaizheng YuAlan B ZondermanDiane M BeckerPaul ElliottTõnu EskoChristian GiegerHans Jörgen GrabeTimo A LakkaTerho LehtimäkiKari E NorthBrenda W J H PenninxPeter VollenweiderLynne E WagenknechtTangchun WuYong-Bing XiangQuan LongDonna K ArnettClaude BouchardMichele K EvansVilmundur G GudnasonSharon KardiaTanika N KellyStephen B KritchevskyRuth J F LoosAlexandre C PereiraMike ProvinceBruce M PsatyCharles RotimiXiaofeng ZhuNajaf AminL Adrienne CupplesMyriam FornageErvin F FoxXiuqing GuoW James GaudermanKenneth RiceCharles KooperbergPatricia B MunroeChing-Ti LiuAlanna C MorrisonDabeeru C RaoDiana van HeemstSusan RedlinePublished in: Nature communications (2019)
Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.