Researchers in Japan made significant strides in understanding the genetic underpinnings of AF, providing not only valuable insights into the disease but also open doors for personalised treatments and advancements in precision medicine.
In the hidden realm of the heart, where its rhythm dances to an intricate tune, lies a common cardiac arrhythmia known as atrial fibrillation (AF), with its grip extending to approximately 46.3 million people worldwide. Despite advancements in diagnostics and treatment, AF often leads to life-threatening complications like stroke and heart failure, placing a substantial burden on patients and healthcare systems.
Recent studies have shed light on the genetic contributions to AF development; however, these studies have predominantly focused on European populations, leaving a knowledge gap regarding the genetic pathophysiology of AF in other populations.
To bridge this gap, a team of researchers conducted a large-scale Japanese genome-wide association study (GWAS) to explore the genetic architecture of AF in a non-European population. They then performed a cross-ancestry meta-analysis, combining data from over 1 million individuals, including 77,690 AF cases. The meta-analysis led to the discovery of 35 new susceptibility loci associated with AF, shedding light on the genetic factors underlying the condition.
“We identified the IL6R gene as a putative causal gene, suggesting the involvement of immune responses in AF development,” shared lead author of the study Kazuo Miyazawa, from the RIKEN Center for Integrative Medical Sciences. “By integrating chromatin immunoprecipitation sequencing (ChIP-seq) data and conducting functional assessments using human induced pluripotent stem cell-derived cardiomyocytes, we also discovered that ERRg, a transcription factor, plays a key role in the regulation of genes associated with AF.”
One significant outcome of this study is the development of a polygenic risk score (PRS) derived from the cross-ancestry meta-analysis. This PRS can predict an individual’s risk of AF and its associated complications. Analysis revealed that individuals with higher PRS had increased risks of cardiovascular and stroke mortalities. Importantly, the PRS was able to identify undiagnosed AF patients at risk of cardioembolic stroke.
The team’s findings, published in Nature Genetics, have demonstrated the clinical utility of the AF-PRS and enhanced our understanding of the disease’s biological mechanisms—promising a future for those impacted by this widespread cardiac condition.