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Gustav Smith

Associate professor

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Heritability of Atrial Fibrillation

Author

  • 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

Summary, in English

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.

Department/s

  • Cardiology
  • Cardiovascular Epigenetics
  • Molecular Epidemiology and Cardiology
  • Heart Failure and Mechanical Support
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2017-12-01

Language

English

Publication/Series

Circulation: Cardiovascular Genetics

Volume

10

Issue

6

Document type

Journal article

Publisher

American Heart Association

Topic

  • Medical Genetics
  • Cardiac and Cardiovascular Systems

Keywords

  • atrial fibrillation
  • epidemiology
  • genome-wide association study
  • genomics
  • medical records

Status

Published

Research group

  • Cardiovascular Epigenetics
  • Molecular Epidemiology and Cardiology
  • Heart Failure and Mechanical Support

ISBN/ISSN/Other

  • ISSN: 1942-325X