Atrial Fibrillation

Illustration showing Atrial Fibrillation and Left Anterior Fasicular Block / Popfossa

New variants linked to atrial fibrillation risk, including several that appear to be specific to East Asian populations, have been discovered. The research is described in two separate studies, both published in Nature Genetics (1 and 2) and which used genome wide association studies and meta-analyses to identify 18 new variants in total.

Atrial fibrillation is a type of cardiac arrhythmia and affects an estimated 33 million people worldwide, increasing the risk of stroke, heart failure, and death. Despite being relatively widespread, previous research has only managed to identify a dozen or so variants associated with risk of the condition in European populations and only one in Asians.

These two new studies were able to expand this knowledge. The first paper identified 12 new loci in a generalised population, and the second focused on people of Japanese descent to establish 2 new population-specific loci.

“Because of the complex [linkage disequilibrium] structure and varying environmental exposures among different populations, it is essential to identify risk factors associated with atrial fibrillation in specific populations, as these could subsequently facilitate better risk prediction for atrial fibrillation in regional clinical settings,” the authors of the second paper wrote.

The first paper, led by researchers from the Atrial Fibrillation Genetics (AFGen) Consortium, used genome and exome wide association studies, alongside rare variant association studies across 22,300 cases and 132,000 controls. 7 of the 12 loci discovered had been linked to related phenotypes, such as electrocardiographic traits and stroke, and a number of nearby genes were shown to encode potassium or sodium channels. 1 of the variants, SH3PXD2A, was specific to participants of Asian ancestry.

The second paper also used a genome wide association study, this time across 8,180 cases and 28,612 controls within the Japanese population. After the initial investigation, they followed up their results in a further 3,120 cases and 125,000 controls. Their research identified 6 new loci, one of which was near SH3PXD2A.

The team also investigated the significance of association for these variants, revealing that the most strongly associated locus was within the HAND2 gene, which encompasses two independent association signals. When functional, HAND2 encodes a protein involved in cardiac morphogenetics.

These studies have greatly advanced our understanding of the genetics of atrial fibrillation and in particular the significance of SH3PXD2A, but both groups acknowledge more work is necessary before their research is actionable.

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