Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis.

J Intern Med
Authors
Keywords
Abstract

BACKGROUND: Genetic polymorphisms associated with common aetiologically complex diseases have recently been identified through genome-wide association studies. Direct-to-consumer genetic testing for such polymorphisms, with provision of absolute genetic risk estimates, is marketed by several commercial companies. Polymorphisms associated with atrial fibrillation (AF) have shown relatively large risk estimates, but the robustness of such estimates across populations and study designs has not been investigated.

DESIGN: A systematic literature review with meta-analysis and assessment of between-study heterogeneity was carried out for single-nucleotide polymorphisms (SNPs) in the six genetic regions associated with AF in genome-wide or candidate gene studies.

RESULTS: Data were identified from 18 samples of European ancestry (n=12,100 cases, 115,702 controls) for the single-nucleotide polymorphisms (SNP) on chromosome 4q25 (rs220733), from 16 samples (n=12,694 cases, 132,602 controls) for the SNP on 16q22 (rs2106261) and from four samples (n=5272 cases, 59,725 controls) for the SNP in KCNH2 (rs1805123). Only the publications in which the associations were initially reported were identified for SNPs on 1q21 and in GJA5 and IL6R, why meta-analyses were not performed for those SNPs. In overall random-effects meta-analyses, association with AF was observed for both SNPs on chromosomes 4q25 [odds ratio (OR), 1.67; 95% CI, 1.50-1.86, P=2×10(-21)] and 16q22 (OR, 1.21; 95% CI, 1.13-1.29, P=1×10(-8)) from genome-wide studies, but not the SNP in KCNH2 from candidate gene studies (P=0.15). There was substantial effect heterogeneity across case-control and cross-sectional studies for both polymorphisms (I(2)=0.50-0.78, P

CONCLUSIONS: In meta-analyses including up to 150,000 individuals, polymorphisms in two genetic regions were robustly associated with AF across all study designs but with substantial context-dependency of risk estimates.

Year of Publication
2012
Journal
J Intern Med
Volume
272
Issue
6
Pages
573-82
Date Published
2012 Dec
ISSN
1365-2796
URL
DOI
10.1111/j.1365-2796.2012.02563.x
PubMed ID
22690879
PubMed Central ID
PMC3763745
Links
Grant list
282255 / European Research Council / International
K23 HL080025 / HL / NHLBI NIH HHS / United States
K23-HL-080025 / HL / NHLBI NIH HHS / United States