Heritability of Atrial Fibrillation

Area of Science:

• Genetics
• Cardiovascular Disease
• Bioinformatics

Background:

• Previous studies identified genetic loci for atrial fibrillation (AF), but genome-wide variation's contribution to AF susceptibility remained unquantified.
• Understanding the genetic architecture of AF is crucial for developing targeted prevention and treatment strategies.

Purpose of the Study:

• To quantify the contribution of genome-wide single-nucleotide polymorphism (SNP) variation to AF risk.
• To investigate the role of common versus rare variants and known AF susceptibility loci in AF heritability.

Main Methods:

• Utilized a variance components method to estimate SNP heritability (h²g) for AF.
• Analyzed data from 120,286 unrelated European ancestry individuals in the UK Biobank, with AF ascertained through multiple sources.
• Focused on variants with a minor allele frequency ≥1% and evaluated h²g across different age and sex strata.

Main Results:

• Genome-wide SNP variation explained 22.1% of AF heritability (h²g), with similar contributions across age and sex.
• Common variants (minor allele frequency ≥5%) accounted for the majority of genetic risk (20.4%).
• Established AF susceptibility, cardiac arrhythmia, and cardiomyopathy gene regions explained only a small proportion (6.4%) of AF variance.

Conclusions:

• Genetic variation plays a substantial role in AF risk, comparable to other cardiovascular diseases.
• The findings underscore the importance of common genetic variants in AF etiology.
• Further genetic discovery, particularly focusing on common variation, is necessary to fully elucidate the causal genetic basis of AF.