Genome-wide association study of electrocardiographic conduction measures in an isolated founder population: Kosrae.

Heart Rhythm
Authors
Keywords
Abstract

BACKGROUND: Cardiac conduction, as assessed by electrocardiographic PR interval and QRS duration, is an important electrophysiological trait and a determinant of arrhythmia risk.

OBJECTIVE: We sought to identify common genetic determinants of these measures.

METHODS: We examined 1604 individuals from the island of Kosrae, Federated States of Micronesia, an isolated founder population. We adjusted for covariates and estimated the heritability of quantitative electrocardiographic QRS duration and PR interval and, secondarily, its subcomponents, P-wave duration and PR segment. Finally, we performed a genome-wide association study (GWAS) in a subset of 1262 individuals genotyped using the Affymetrix GeneChip Human Mapping 500K microarray.

RESULTS: The heritability of PR interval was 34% (standard error [SE] 5%, P = 4 x 10(-18)); of PR segment, 31% (SE 6%, P = 3.2 x 10(-13)); and of P-wave duration, 17% (SE 5%, P = 5.8 x 10(-6)), but the heritablility of QRS duration was only 3% (SE 4%, P = .20). Hence, GWAS was performed only for the PR interval and its subcomponents. A total of 338,049 single nucleotide polymorphisms (SNPs) passed quality filters. For the PR interval, the most significantly associated SNPs were located in and downstream of the alpha-subunit of the cardiac voltage-gated sodium channel gene SCN5A, with a 4.8 ms (SE 1.0) or 0.23 standard deviation increase in adjusted PR interval for each minor allele copy of rs7638909 (P = 1.6 x 10(-6), minor allele frequency 0.40). These SNPs were also associated with P-wave duration (P = 1.5 x 10(-4)) and PR segment (P = .01) but not with QRS duration (P > or =.22).

CONCLUSIONS: The PR interval and its subcomponents showed substantial heritability in a South Pacific islander population and were associated with common genetic variation in SCN5A.

Year of Publication
2009
Journal
Heart Rhythm
Volume
6
Issue
5
Pages
634-41
Date Published
2009 May
ISSN
1556-3871
URL
DOI
10.1016/j.hrthm.2009.02.022
PubMed ID
19389651
PubMed Central ID
PMC2673462
Links
Grant list
K23 HL080025 / HL / NHLBI NIH HHS / United States
K23 HL080025-04 / HL / NHLBI NIH HHS / United States
Howard Hughes Medical Institute / United States
K23-HL-080025 / HL / NHLBI NIH HHS / United States