6533b82efe1ef96bd1292992
RESEARCH PRODUCT
Large-scale association analysis identifies new risk loci for coronary artery disease
Benjamin F. VoightAndrew D. MorrisG. Kees HovinghAnthony J. BalmforthHanneke BasartAlistair S. HallDominique GauguierDominique GauguierBok Ghee HanMartina Müller-nurasyidSarah ParishJarmo VirtamoChrista MeisingerPeter WagnerPeter WagnerGeorge DedoussisPhilipp S. WildKari StefanssonKari StefanssonJean-baptiste CazierKathleen StirrupsJiyoung LeeAdrienne CupplesAdrienne CupplesStavroula KanoniDanish SaleheenDanish SaleheenChristian HengstenbergSvati H. ShahPanos DeloukasAnuj GoelStefan BlankenbergSian Tsung TanAlison H. GoodallAlison H. GoodallTõnu EskoEric BoerwinkleGudmundur ThorgeirssonPeter S. BraundPeter S. BraundJoshua W. KnowlesOlle MelanderC. Ellen Van Der SchootSilke RosingerMaria DimitriouWolfgang KoenigMichael BoehnkeFrançois CambienPer LundmarkDmitry ShunginDmitry ShunginWolfgang KratzerPierre ZallouaReijo LaaksonenJean FerrièresVilli GudnasonThorsten KesslerDaniel J. RaderNiclas ErikssonDominique ArveilerNatalie R. Van ZuydamKuulasmaa KariN. William RaynerSarah E. HuntGudmar ThorleifssonJeanette ErdmannSamuli RipattiSamuli RipattiTsun-po YangGeorge A. WellsTerho LehtimäkiKjell NikusPierre FontanillasJorg HagerMartin FarrallJemma C. HopewellFrank KeeJuha SinisaloChristopher J. O'donnellAsif RasheedMika KähönenGenovefa KolovouSeraya MaoucheSuzanne RafeltCordelia LangfordWinfried MärzWinfried MärzLeo-pekka LyytikäinenChristina WillenborgWeihua ZhangKati KristianssonHyo-soo KimWeang K. HoJeong E. ParkMohan U. SivananthanMoritz P. RumpfMarkku LaaksoKlaus StarkPhilippe AmouyelPaul W. FranksPaul W. FranksPaul W. FranksAndres MetspaluAnders Franco-cerecedaManjinder S. SandhuManjinder S. SandhuNour Eddine El MokhtariNicholas J. WarehamRobert RobertsVeikko SalomaaThomas IlligTomi PastinenRobert ClarkeChristof BurgdorfLeif GroopDevin AbsherYangsoo JangMark I. MccarthyBernhard O. BoehmPer ErikssonNilesh J. SamaniNilesh J. SamaniInke R. KönigStefan SchreiberKarin LeanderSimone Claudi-boehmCi SongBenjamin A. GoldsteinStephen E. EpsteinAndreas ZieglerStanley L. HazenArne SchäferElin GrundbergSekar KathiresanSekar KathiresanJohn R. ThompsonUnnur ThorsteinsdottirUnnur ThorsteinsdottirMuredach P. ReillyHeribert SchunkertRory CollinsThomas QuertermousJong-young LeeJohn DaneshJohn C. ChambersMarco M FerrarioCarlos IribarrenClaudia LangenbergHilma HolmRona J. StrawbridgeAlan S. GoCristen J. WillerRon DoRon DoEmmi TikkanenEmmi TikkanenAbbas DehghanEvelin MihailovLindsay L. WaitePatrick DiemertWillem H. OuwehandWillem H. OuwehandWillem H. OuwehandEric E. SchadtDiana RubinDavid AltshulerDavid AltshulerMarcus E. KleberMarkus PerolaAlexandre F.r. StewartJaspal S. KoonerThemistocles L. AssimesInês BarrosoInês BarrosoBruna GiganteGöran HallmansMarja-liisa LokkiAki S. HavulinnaAnders HamstenAgneta SiegbahnLasse FolkersenErik IngelssonMartina E. ZimmermannColin N. A. PalmerPaolo BrambillaAnn-christine SyvänenAlun EvansÅSa JohanssonJohn F. PedenAlex S. F. DoneyHugh WatkinsJohanna KuusistoAnders LundmarkDavid G. CoxHyun Min KangLars LindKrista FischerMarkku S. NieminenAnnette PetersNorman KloppStefan GustafssonLars WallentinNancy L. PedersenDavid-alexandre TrégouëtUlf De Fairesubject
AdultAsian Continental Ancestry GroupMaleCandidate geneBIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICAPopulationEuropean Continental Ancestry GroupQuantitative Trait LociCADGenome-wide association studySingle-nucleotide polymorphismCoronary Artery Disease030204 cardiovascular system & hematologyBiologyQuantitative trait locusBioinformaticsPolymorphism Single NucleotideArticleWhite Peoplecoronary artery disease risk lociCell LineCoronary artery disease03 medical and health sciences0302 clinical medicineAsian PeopleRisk FactorsmedicineHumansgeneticsGene Regulatory NetworksGenetic Predisposition to Diseasecardiovascular diseasesPolymorphismeducation030304 developmental biologyGenetic associationAgedGenetics0303 health scienceseducation.field_of_studyAdult Aged Asian Continental Ancestry Group Cell Line Coronary Artery Disease; genetics European Continental Ancestry Group; genetics Female Gene Regulatory Networks Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Middle Aged Polymorphism; Single Nucleotide Quantitative Trait Loci Risk FactorsSingle NucleotideMiddle Agedmedicine.disease3. Good healthFemaleGenome-Wide Association Studydescription
Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r 2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways. © 2013 Nature America, Inc. All rights reserved.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-07-28 | Nature Genetics |