Journal article
A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
Human molecular genetics, Vol.28(15), pp.2615-2633
08/01/2019
DOI: 10.1093/hmg/ddz070
PMCID: PMC6644157
PMID: 31127295
Abstract
Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
Details
- Title: Subtitle
- A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- Creators
- Yun Ju Sung - Washington University in St. Louis School of MedicineLisa de las Fuentes - Washington University in St. Louis School of MedicineThomas W Winkler - University of RegensburgDaniel I Chasman - Brigham and Women's HospitalAmy R Bentley - National Human Genome Research InstituteAldi T Kraja - Washington University in St. Louis School of MedicineIoanna Ntalla - Queen Mary University of LondonHelen R Warren - Queen Mary University of LondonXiuqing Guo - Harbor–UCLA Medical CenterKaren Schwander - Washington University in St. Louis School of MedicineAlisa K Manning - Massachusetts General HospitalMichael R Brown - The University of Texas Health Science Center at HoustonHugues Aschard - Harvard UniversityMary F Feitosa - Washington University in St. Louis School of MedicineNora FranceschiniYingchang LuChing-Yu ChengXueling SimDina VojinovicJonathan MartenSolomon K MusaniTuomas O KilpeläinenMelissa A RichardStella AslibekyanTraci M BartzRajkumar Dorajoo - Genome Institute of SingaporeChangwei Li - University of GeorgiaYongmei LiuTuomo RankinenAlbert Vernon SmithSalman M TajuddinBamidele O TayoWei ZhaoYanhua ZhouNana MatobaTamar SoferMaris AlverMarzyeh AminiMathilde BoisselJin Fang ChaiXu ChenJasmin DiversIlaria GandinChuan GaoFranco GiulianiniAnuj GoelSarah E HarrisFernando P HartwigMeian HeAndrea R V R HorimotoFang-Chi HsuAnne U JacksonCandace M KammererAnuradhani KasturiratnePirjo KomulainenBrigitte KühnelKarin LeanderWen-Jane LeeKeng-Hung LinJian’an LuanLeo-Pekka LyytikäinenColin A McKenzieChristopher P NelsonRaymond NoordamWayne H H SheuAlena StančákováFumihiko TakeuchiPeter J van der MostTibor V VargaRobert J WakenHeming WangYajuan WangErin B WareStefan WeissWanqing WenLisa R YanekWeihua ZhangSaima AfaqTamuno AlfredDan E ArkingTin AungNajaf AminR Graham BarrLawrence F BielakEric BoerwinkleErwin P BottingerPeter S BraundJennifer A BrodyUlrich BroeckelBrian CadeArchie CampbellMickaël CanouilAravinda ChakravartiMassimiliano CoccaFrancis S CollinsJohn M ConnellRenée de MutsertH Janaka de SilvaMarcus DörrQing DuanCharles B EatonGeorg EhretEvangelos EvangelouJessica D FaulNita G ForouhiOscar H FrancoYechiel FriedlanderHe GaoBruna GiganteC Charles GuPreeti GuptaSaskia P HagenaarsTamara B HarrisJiang HeSami HeikkinenChew-Kiat HengAlbert HofmanBarbara V HowardSteven C HuntMarguerite R IrvinTomohiro KatsuyaJoel KaufmanNicola D KerrisonChiea Chuen KhorWoon-Puay KohHeikki A KoistinenCharles B KooperbergJose E KriegerMichiaki KuboZoltan KutalikJohanna KuusistoTimo A LakkaCarl D LangefeldClaudia LangenbergLenore J LaunerJoseph H LeeBenjamin LehneDaniel LevyCora E LewisChing-Ti LiuJianjun LiuJingmin LiuSing Hui LimMarie LohKurt K LohmanTin LouieReedik MägiKoichi MatsudaThomas MeitingerAndres MetspaluLili MilaniYukihide MomozawaThomas H Mosley JrMike A NallsUbaydah NasriJeff R O'ConnellAdesola OgunniyiWalter R PalmasNicholette D PalmerNancy L PedersenAnnette PetersPatricia A PeyserOzren PolasekDavid PorteousOlli T RaitakariJames S PankowFrida RenströmTreva K RicePaul M RidkerAntonietta RobinoJennifer G RobinsonLynda M RoseIgor RudanCharumathi SabanayagamBabatunde L SalakoKevin SandowCarsten O SchmidtPamela J SchreinerPeter SeverMario SimsColleen M SitlaniJennifer A SmithHarold SniederJohn M StarrKonstantin StrauchHua TangKent D TaylorYik Ying TeoYih Chung ThamAndré G UitterlindenMelanie WaldenbergerLihua WangYa Xing WangWen Bin WeiGregory WilsonMary K WojczynskiYong-Bing XiangJie YaoJian-Min YuanAlan B ZondermanDiane M BeckerMichael BoehnkeDonald W BowdenJohn C ChambersYii-Der Ida ChenDavid R WeirUlf de FaireIan J DearyTõnu EskoMartin FarrallTerrence ForresterBarry I FreedmanPhilippe FroguelMarkku LaaksoPaolo GaspariniTerho LehtimäkiChristian GiegerKae-Woei LiangBernardo Lessa HortaPatrik K E MagnussonAlbertine J OldehinkelYi-Jen HungJost Bruno JonasAlexandre C PereiraNorihiro KatoThomas PerlsRainer RauramaaJaspal S KoonerSusan RedlineRainer RettigNilesh J SamaniXiao-Ou ShuPim van der HarstLynne E WagenknechtNicholas J WarehamHugh WatkinsAnanda R WickremasingheTangchun WuYoichiro KamataniCathy C LaurieClaude BouchardRichard S CooperMichele K EvansVilmundur GudnasonJames HixsonSharon L R KardiaStephen B KritchevskyBruce M PsatyRob M van DamDonna K ArnettDennis O Mook-KanamoriMyriam FornageCharles N RotimiErvin R FoxLaura J Bierut - Washington University in St. Louis School of MedicineCaroline HaywardXiaofeng ZhuL Adrienne CupplesCornelia M van DuijnE Shyong TaiMichael A ProvinceJerome I RotterTien Yin WongPaul W FranksRuth J F LoosAlex P ReinerKenneth RicePaul ElliottMark J CaulfieldW James GaudermanPatricia B MunroeDabeeru C RaoLifelines Cohort StudyWilliam R ScottYucheng Jia - Harbor–UCLA Medical CenterBlair H SmithAlanna C MorrisonJing Hua ZhaoYeheng Liu - Harbor–UCLA Medical CenterRobert A ScottJames ScottYize Li
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.28(15), pp.2615-2633
- DOI
- 10.1093/hmg/ddz070
- PMID
- 31127295
- PMCID
- PMC6644157
- NLM abbreviation
- Hum Mol Genet
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Publisher
- Oxford University Press
- Grant note
- R01HL118305 / ; ; ;
- Language
- English
- Date published
- 08/01/2019
- Academic Unit
- Epidemiology; Internal Medicine
- Record Identifier
- 9983995134802771
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