PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.
Jessica van SettenJennifer A BrodyYalda JamshidiBrenton R SwensonAnne M ButlerHarry CampbellFabiola M Del GrecoDaniel S EvansQuince GibsonDaniel F GudbjartssonKathleen F KerrBouwe P KrijtheLeo-Pekka LyytikainenChristian MüllerMartina Müller-NuraysidIlja Maria NolteSandosh PadmanabhanMarylyn DeRiggi RitchieAntonietta RobinoAlbert Vernon SmithMaristella SteriToshiko TanakaAlexander TeumerStella TrompetSheila UliviNiek VerweijXiaoyan YinDavid O ArnarFolkert W. AsselbergsJoel S BaderJohn BarnardJosh BisStefan BlankenbergEric BoerwinkleYuki BradfordBrendan M BuckleyMina K ChungDana CrawfordMarcel den HoedJosh C DennyAnna F DominiczakGeorg B EhretMark EijgelsheimPatrick T EllinorStephan B FelixOscar H FrancoLude H FrankeTamara B HarrisHilma HolmGandin IlariaAnnamaria IorioMika KähönenIvana KolcicJan A KorsEdward G LakattaLenore J LaunerHonghuang LinHenry J LinRuth J F LoosSteven A LubitzPeter W MacfarlaneJared W MagnaniIrene Mateo LeachThomas MeitingerBraxton D MitchellThomas MunzelGeorge J PapanicolaouAnnette PetersArne PfeuferPeter P PramstallerOlli T RaitakariJerome I RotterIgor RudanNilesh J SamaniDavid SchlessingerClaudia T Silva AldanaMoritz F SinnerJonathan D SmithHarold SniederElsayed Z SolimanTimothy D SpectorDavid J StottKonstantin StrauchKirill V TarasovUnnur ThorsteinsdottirAndre G UitterlindenDavid R Van WagonerUwe VölkerHenry VölzkeMelanie WaldenbergerHarm-Jan WestraPhilipp S WildTanja ZellerAlvaro AlonsoChristy L AveryStefania BandinelliEmelia J BenjaminFrancesco CuccaMarcus DörrLuigi FerrucciPaolo GaspariniVilmundur GudnasonCaroline HaywardSusan R HeckbertAndrew A HicksJohan Wouter JukemaStefan KääbTerho LehtimäkiYongmei LiuPatricia B MunroeAfshin ParsaOzren PolasekBruce M PsatyDan M RodenRenate B SchnabelGianfranco SinagraKari StefanssonBruno H StrickerPim van der HarstCornelia M van DuijnJames F WilsonSina A GharibPaul I W de BakkerAaron IsaacsDan E ArkingNona SotoodehniaPublished in: Nature communications (2018)
Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
Keyphrases
- genome wide
- atrial fibrillation
- catheter ablation
- genome wide association study
- genome wide association
- left atrial
- copy number
- dna methylation
- heart failure
- heart rate
- left ventricular
- left atrial appendage
- oral anticoagulants
- systematic review
- direct oral anticoagulants
- single cell
- heart rate variability
- transcription factor
- percutaneous coronary intervention
- poor prognosis
- cell therapy
- venous thromboembolism
- rna seq
- stem cells
- coronary artery disease
- intellectual disability
- genome wide identification
- acute coronary syndrome
- long non coding rna
- bone marrow
- risk assessment
- randomized controlled trial
- meta analyses