Heritability of Atrial Fibrillation. (December 2017)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Circulation. Volume 10:Number 6(2017)
• Publication Date: 2017-12
• Subjects: atrial fibrillation -- epidemiology -- genome-wide association study -- genomics -- medical records; Arrhythmia -- Periodicals; Heart -- Electric properties -- Periodicals; 616.1042
• DOI: 10.1161/CIRCGENETICS.117.001838
• Languages: English
• ISSNs: 1942-325X

Abstract

Abstract : Background—: Previous reports have implicated multiple genetic loci associated with AF, but the contributions of genome-wide variation to AF susceptibility have not been quantified. Methods and Results—: We assessed the contribution of genome-wide single-nucleotide polymorphism variation to AF risk (single-nucleotide polymorphism heritability, h 2 g ) 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 h 2 g using a variance components method with variants having a minor allele frequency ≥1%. We evaluated h 2 g in age, sex, and genomic strata of interest. The h 2 g 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. Conclusions—: 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. Abstract : Supplemental Digital Content is available in the text.