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van Setten, J.* ; Verweij, N.* ; Mbarek, H.* ; Niemeijer, M.N.* ; Trompet, S.* ; Arking, D.E.* ; Brody, J.A.* ; Gandin, I.* ; Grarup, N.* ; Hall, L.M.* ; Hemerich, D.* ; Lyytikäinen, L.P.* ; Mei, H.* ; Müller-Nurasyid, M. ; Prins, B.P.* ; Robino, A.* ; Smith, A.V.* ; Warren, H.R.* ; Asselbergs, F.W.* ; Boomsma, D.I.* ; Caulfield, M.J.* ; Eijgelsheim, M.* ; Ford, I.* ; Hansen, T.* ; Harris, T.B.* ; Heckbert, S.R.* ; Hottenga, J.J.* ; Iorio, A.* ; Kors, J.A.* ; Linneberg, A.* ; Macfarlane, P.W.* ; Meitinger, T. ; Nelson, C.P.* ; Raitakari, O.T.* ; Silva Aldana, C.T.* ; Sinagra, G.* ; Sinner, M.* ; Soliman, E.Z.* ; Stoll, M.* ; Uitterlinden, A.* ; van Duijn, C.M.* ; Waldenberger, M. ; Alonso, A.* ; Gasparini, P.* ; Gudnason, V.* ; Jamshidi, Y.* ; Kääb, S.* ; Kanters, J.K.* ; Lehtimäki, T.* ; Munroe, P.B.* ; Peters, A. ; Samani, N.J.* ; Sotoodehnia, N.* ; Ulivi, S.* ; Wilson, J.G.* ; de Geus, E.J.C.* ; Jukema, J.W.* ; Stricker, B.* ; van der Harst, P.* ; de Bakker, P.I.W.* ; Isaacs, A.*

Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits.

Eur. J. Hum. Genet. 27, 952-962 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Qt Interval Duration; Glucocorticoid-receptor; Common Variants; Heart-rate; Protein; Phospholamban; Contractility; Polymorphism; Annotation; Mutations
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 1018-4813
e-ISSN 1476-5438
Journal European Journal of Human Genetics
Quellenangaben Volume: 27, Issue: 6, Pages: 952-962 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-500700-001
G-504091-001
G-504000-010
DOI 10.1038/s41431-018-0295-z
WOS ID WOS:000467381900013
Scopus ID 85060589966
PubMed ID 30679814
Erfassungsdatum 2019-03-07
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