| Title: | Heritability of Atrial Fibrillation |
| Journal: | Circulation Genomic and Precision Medicine |
| Published: | 1 Dec 2017 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/29237688/ |
| DOI: | https://doi.org/10.1161/circgenetics.117.001838 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/CIRCGENETICS.117.001838 |
Publication 8500
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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.</p>
METHODS AND RESULTS: We assessed the contribution of genome-wide single-nucleotide polymorphism variation to AF risk (single-nucleotide polymorphism heritability, h2g ) 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 h2g using a variance components method with variants having a minor allele frequency ≥1%. We evaluated h2g in age, sex, and genomic strata of interest. The h2g 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.</p>
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.</p>
15 Authors
- Lu-Chen Weng
- Seung Hoan Choi
- Derek Klarin
- J Gustav Smith
- Po-Ru Loh
- Mark Chaffin
- Carolina Roselli
- Olivia L Hulme
- Kathryn L Lunetta
- Josée Dupuis
- Emelia J Benjamin
- Christopher Newton-Cheh
- Sekar Kathiresan
- Patrick T Ellinor
- Steven A Lubitz
1 Application
| Application ID | Title |
|---|---|
| 15293 | Genetic dissection of the relationships of myocardial diseases and their risk factors |
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