Genetic variation “contributes substantially” to AF susceptibility

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A recent study by Lu-Chen Weng (Massachusetts General Hospital, Boston, USA) et al which aimed to quantify and systematically characterise the genetic architecture of atrial fibrillation (AF) has found that genetic variation contributes substantially to AF susceptibility and risk. The study was published in Circulation: Cardiovascular Genetics.

Over 30 genes and 16 loci have previously been implicated in the pathogenesis of AF. The study by Weng et al was designed to address the lack of systematic characterisation of the genetic architecture of the arrhythmia, as well as quantifying the contributions of genome-wide variation to AF susceptibility.

Using data from the population-based UK Biobank, 120,286 unrelated individuals of European ancestry were assessed, 2,987 of which had AF. Previous data shows that European populations have around a doubled prevalence rate of AF compared to African-Americans, pointing towards a genetic predisposition in this group.

The AF risk contribution of genome-wide single-nucleotide polymorphism variation (named h2g by the authors to signify single-nucleotide polymorphism heritibility) was evaluated in age, sex, alelle frequency and established AF loci with ±500 kb of a top associated variant.

The investigators found a 22.1% h2for AF (95% confidence interval, 15.6%–28.5%), which did not vary significantly across age of AF onset or gender. “The proportion of AF variance explained by genetic variation”, Weng et al write, “was mainly accounted for by common (minor allelle frequency, ≥5%) variants (20.4%; 95% confidence interval, 15.1%–25.6%).”

They add that only 6.4% of AF variance (95% confidence interval, 5.1%-7.7%) was attributed to variation within known AF suscptibility, cardiac arrhythmia and cardiomyopathy gene regions. The risk for AF conferred by genomic variation was observed to be similar to that of several other cardiovascular diseases.

 

The fact that AF variance was largely attributed to common variants and only minimally to known AF loci points to the need for further genetic discovery with an emphasis on common variation, the authors suggest, in order to “understand the causal genetic basis of AF.”

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