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Heritability of Atrial Fibrillation

Weng, Lu Chen; Choi, Seung Hoan; Klarin, Derek; Smith, J. Gustav LU ; Loh, Po Ru; Chaffin, Mark; Roselli, Carolina; Hulme, Olivia L.; Lunetta, Kathryn L. and Dupuis, Josée, et al. (2017) In Circulation: Cardiovascular Genetics 10(6).
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, h2 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 h2 g using a variance components method with variants having a minor allele frequency ≥1%. We evaluated... (More)

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, h2 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 h2 g using a variance components method with variants having a minor allele frequency ≥1%. We evaluated h2 g in age, sex, and genomic strata of interest. The h2 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.

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@article{b61033fe-1cfc-4a64-a753-7f671f17e625,
  abstract     = {<p>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<sup>2</sup> <sub>g</sub>) 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<sup>2</sup> <sub>g</sub> using a variance components method with variants having a minor allele frequency ≥1%. We evaluated h<sup>2</sup> <sub>g</sub> in age, sex, and genomic strata of interest. The h<sup>2</sup> <sub>g</sub> for AF was 22.1% (95% confidence interval, 15.6%-28.5%) and was similar for early- versus older-onset AF (≤65 versus &gt;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.</p>},
  articleno    = {e001838},
  author       = {Weng, Lu Chen and Choi, Seung Hoan and Klarin, Derek and Smith, J. Gustav and Loh, Po Ru and Chaffin, Mark and Roselli, Carolina and Hulme, Olivia L. and Lunetta, Kathryn L. and Dupuis, Josée and Benjamin, Emelia J. and Newton-Cheh, Christopher and Kathiresan, Sekar and Ellinor, Patrick T. and Lubitz, Steven A.},
  issn         = {1942-325X},
  keyword      = {atrial fibrillation,epidemiology,genome-wide association study,genomics,medical records},
  language     = {eng},
  month        = {12},
  number       = {6},
  publisher    = {American Heart Association},
  series       = {Circulation: Cardiovascular Genetics},
  title        = {Heritability of Atrial Fibrillation},
  url          = {http://dx.doi.org/10.1161/CIRCGENETICS.117.001838},
  volume       = {10},
  year         = {2017},
}