Heritability of Atrial Fibrillation

Previous reports have implicated multiple genetic loci associated with AF, but the contributions of genome-wide variation to AF susceptibility have not been quantified. We assessed the contribution of genome-wide single-nucleotide polymorphism variation to AF risk (single-nucleotide polymorphism her...

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Vydáno v:Circulation. Cardiovascular genetics Ročník 10; číslo 6
Hlavní autoři: Weng, Lu-Chen, Choi, Seung Hoan, Klarin, Derek, Smith, J Gustav, Loh, Po-Ru, Chaffin, Mark, Roselli, Carolina, Hulme, Olivia L, Lunetta, Kathryn L, Dupuis, Josée, Benjamin, Emelia J, Newton-Cheh, Christopher, Kathiresan, Sekar, Ellinor, Patrick T, Lubitz, Steven A
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.12.2017
Témata:
Aged
Atrial Fibrillation - genetics
Female
Gene Frequency
Genetic Predisposition to Disease - ethnology
Genetic Predisposition to Disease - genetics
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Male
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
United Kingdom
White People - genetics
United Kingdom
epidemiology
genomics
atrial fibrillation
medical records
genome-wide association study
ISSN:1942-3268, 1942-3268
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Shrnutí:Previous reports have implicated multiple genetic loci associated with AF, but the contributions of genome-wide variation to AF susceptibility have not been quantified. We assessed the contribution of genome-wide single-nucleotide polymorphism variation to AF risk (single-nucleotide polymorphism heritability, ) using data from 120 286 unrelated individuals of European ancestry (2987 with AF) in the population-based UK Biobank. We ascertained AF based on self-report, medical record billing codes, procedure codes, and death records. We estimated using a variance components method with variants having a minor allele frequency ≥1%. We evaluated in age, sex, and genomic strata of interest. The for AF was 22.1% (95% confidence interval, 15.6%-28.5%) and was similar for early- versus older-onset AF (≤65 versus >65 years of age), as well as for men and women. The proportion of AF variance explained by genetic variation was mainly accounted for by common (minor allele frequency, ≥5%) variants (20.4%; 95% confidence interval, 15.1%-25.6%). Only 6.4% (95% confidence interval, 5.1%-7.7%) of AF variance was attributed to variation within known AF susceptibility, cardiac arrhythmia, and cardiomyopathy gene regions. Genetic variation contributes substantially to AF risk. The risk for AF conferred by genomic variation is similar to that observed for several other cardiovascular diseases. Established AF loci only explain a moderate proportion of disease risk, suggesting that further genetic discovery, with an emphasis on common variation, is warranted to understand the causal genetic basis of AF.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1942-3268
1942-3268
DOI:10.1161/CIRCGENETICS.117.001838