Heritability of Atrial Fibrillation.
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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, ) 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. 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. |
Year of Publication | 2017
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Journal | Circ Cardiovasc Genet
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Volume | 10
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Issue | 6
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Date Published | 2017 Dec
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ISSN | 1942-3268
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DOI | 10.1161/CIRCGENETICS.117.001838
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PubMed ID | 29237688
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PubMed Central ID | PMC5966046
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Grant list | K24 HL105780 / HL / NHLBI NIH HHS / United States
2014105 / DDCF / Doris Duke Charitable Foundation / United States
K23 HL114724 / HL / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
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