GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.
Nora FranceschiniClaudia GiambartolomeiPaul S de VriesChris FinanJoshua C BisRachael P HuntleyRuth C LoveringSalman M TajuddinThomas W WinklerMisa GraffMaryam KavousiCaroline DaleAlbert V SmithEdith HoferElisabeth M van LeeuwenIlja Maria NolteLingyi LuMarkus ScholzMuralidharan SargurupremrajNiina PitkänenOscar FranzénPeter K JoshiRaymond NoordamRiccardo E MarioniShih-Jen HwangSolomon K MusaniUlf SchminkeWalter PalmasAaron IsaacsAdolfo CorreaAlan B ZondermanAlbert HofmanAlexander TeumerAmanda J CoxAndré G UitterlindenAndrew WongAndries J SmitAnne B NewmanAnnie BrittonArno RuusaleppBengt SennbladBo HedbladBogdan PasaniucBrenda W PenninxCarl D LangefeldChristina L WasselChristophe TzourioCristiano FavaDamiano BaldassarreDaniel H O'LearyDaniel TeupserDiana KuhElena TremoliElmo MannarinoEnzo GrossiEric BoerwinkleEric E SchadtErik IngelssonFabrizio VegliaFernando RivadeneiraFrank BeutnerGanesh ChauhanGerardo HeissHarold SniederHarry CampbellHenry VölzkeHugh S MarkusIan J DearyJohan Wouter JukemaJacqueline de GraafJacqueline PriceJanne PottJemma C HopewellJingjing LiangJoachim ThieryJorgen EngmannKarl GertowKenneth M RiceKent D TaylorKlodian DhanaLambertus A L M KiemeneyLars LindLaura M RaffieldLenore J LaunerLesca M HoldtMarcus DörrMartin DichgansMatthew TraylorMatthias SitzerMeena KumariMika KivimakiMike A NallsOlle MelanderOlli RaitakariOscar H FrancoOscar L Rueda-OchoaPanagiotis RoussosPeter H WhincupPhillippe AmouyelPhilippe GiralPramod AnuguQuenna WongRainer MalikRainer RauramaaRalph BurkhardtRebecca HardyReinhold SchmidtRenée de MutsertRichard W MorrisRona J StrawbridgeS Goya WannametheeSara HäggSonia ShahStela McLachlanStella TrompetSudha SeshadriSudhir KurlSusan R HeckbertSusan RingTamara B HarrisTerho LehtimäkiTessel E GaleslootTina ShahUlf de FaireVincent PlagnolWayne D RosamondWendy PostXiaofeng ZhuXiaoling ZhangXiuqing GuoYasaman Sabanull nullAbbas DehghanAdrie SeldenrijkAlanna C MorrisonAnders HamstenBruce M PsatyCornelia M van DuijnDeborah A LawlorDennis O Mook-KanamoriDonald W BowdenHelena SchmidtJames F WilsonJames G WilsonJerome I RotterJoanna Marguerite WardlawJohn DeanfieldJulian HalcoxLeo-Pekka LyytikainenMarkus LoefflerMichele K EvansStéphanie DebetteSteve E HumphriesUwe VölkerVilmundur G GudnasonAroon D HingoraniJohan L M BjörkegrenJuan P CasasChristopher J O'DonnellPublished in: Nature communications (2018)
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Keyphrases
- genome wide
- genome wide association
- genome wide association study
- coronary artery disease
- dna methylation
- copy number
- atrial fibrillation
- systematic review
- cardiovascular disease
- meta analyses
- randomized controlled trial
- gene expression
- optical coherence tomography
- metabolic syndrome
- type diabetes
- mass spectrometry
- brain injury
- binding protein
- subarachnoid hemorrhage
- data analysis
- cerebral ischemia
- case control
- bioinformatics analysis