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Title:

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

Document type:
Journal Article; Research Support, Non-U.S. Gov't; Article
Author(s):
van Setten, Jessica; Verweij, Niek; Mbarek, Hamdi; Niemeijer, Maartje N; Trompet, Stella; Arking, Dan E; Brody, Jennifer A; Gandin, Ilaria; Grarup, Niels; Hall, Leanne M; Hemerich, Daiane; Lyytikäinen, Leo-Pekka; Mei, Hao; Müller-Nurasyid, Martina; Prins, Bram P; Robino, Antonietta; Smith, Albert V; Warren, Helen R; Asselbergs, Folkert W; Boomsma, Dorret I; Caulfield, Mark J; Eijgelsheim, Mark; Ford, Ian; Hansen, Torben; Harris, Tamara B; Heckbert, Susan R; Hottenga, Jouke-Jan; Iorio, Annamaria;...     »
Abstract:
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.
Journal title abbreviation:
Eur J Hum Genet
Year:
2019
Journal volume:
27
Journal issue:
6
Pages contribution:
952-962
Fulltext / DOI:
doi:10.1038/s41431-018-0295-z
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/30679814
Print-ISSN:
1018-4813
TUM Institution:
606; 656; 658; Institut für Humangenetik
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