Gustav Smith
Associate professor
Heritability of Atrial Fibrillation
Author
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
Links
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