|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Smith, JG, Almgren, P, Engström, G, Hedblad, B, Platonov, PG, Newton-Cheh, C, Melander, O|
|Journal||J Intern Med|
|Date Published||2012 Dec|
|Keywords||Atrial Fibrillation, Chromosome Mapping, Chromosomes, Human, Pair 4, Genetic Markers, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Humans, Models, Statistical, Polymorphism, Single Nucleotide, Risk Assessment|
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.
|Alternate Journal||J. Intern. Med.|
|PubMed Central ID||PMC3763745|
|Grant List||282255 / / European Research Council / International |
K23 HL080025 / HL / NHLBI NIH HHS / United States
K23-HL-080025 / HL / NHLBI NIH HHS / United States