Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits.
Jessica van SettenNiek VerweijHamdi MbarekMaartje N NiemeijerStella TrompetDan E ArkingJennifer A BrodyIlaria GandinNiels GrarupLeanne M HallDaiane HemerichLeo-Pekka LyytikäinenHao MeiMartina Müller-NuraysidBram P PrinsAntonietta RobinoAlbert V SmithHelen R WarrenFolkert W. AsselbergsDorret I BoomsmaMark J CaulfieldMark EijgelsheimIan FordTorben HansenTamara B HarrisSusan R HeckbertJouke-Jan HottengaAnnamaria IorioJan A KorsAllan LinnebergPeter W MacFarlaneThomas MeitingerChristopher P NelsonOlli T RaitakariClaudia T Silva AldanaGianfranco SinagraMoritz SinnerElsayed Z SolimanMonika StollAndre UitterlindenCornelia M van DuijnMelanie WaldenbergerAlvaro AlonsoPaolo GaspariniVilmundur GudnasonYalda JamshidiStefan KääbJørgen Kim KantersTerho LehtimäkiPatricia B MunroeAnnette PetersNilesh J SamaniNona SotoodehniaSheila UliviJames G WilsonEco J C N de GeusJohan Wouter JukemaBruno StrickerPim van der HarstPaul I W de BakkerAaron IsaacsPublished in: European journal of human genetics : EJHG (2019)
Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits: PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency < 5%). In addition to many known loci, we identified seven novel locus-trait associations: KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes.
Keyphrases
- genome wide association
- genome wide
- heart rate
- dna methylation
- heart rate variability
- systematic review
- blood pressure
- high resolution
- drug induced
- left ventricular
- cardiac resynchronization therapy
- heart failure
- randomized controlled trial
- genome wide association study
- case control
- transcription factor
- big data
- atrial fibrillation
- meta analyses
- mitral valve