Japanese researchers conduct largest ever genetic study on heart arrhythmia

Researchers at the RIKEN Center for Integrative Medical Sciences based in Japan have conducted the largest genetic study ever on heart arrhythmia.

According to the RIKEN website, the results were published in the scientific journal Nature Genetics. 

The team was led by Kazuo Miyazawa and Kaoru Ito who analyzed data from more than 1 million people to discover genes and individual genetic variations associated with atrial fibrillation. Atrial fibrillation is when the heart beats rapidly and irregularly, and it leads to blood clots in the atria. It increases the risk of blood clots to the brain and causes strokes. 

Although atrial fibrillation has been associated with genetic factors, the study showed that the exact mechanisms behind it are still unclear.

“Until now which genes and how their transcriptional regulation is involved in the pathophysiology of atrial fibrillation was not very clear,” Miyazawa said. “In this study we discovered a key mechanism by integrating genomic data with epigenomic and transcriptomic data.”

The report on the website noted that genomes from more than 150,000 people from Japan were studied. Give genetic loci that were previously unidentified with atrial fibrillation were identified. These included two with genetic variations unique to East Asian people. More than 1.2 million people were then analyzed with a cross-ancestry meta-analysis that came up with 150 genetic loci. This included 35 that were new.

More than 140 genes associated with the loci were also found, showing it is most likely that variations in one or several genes leads to atrial fibrillation. The team also found transcription factor ERRg to be associated with genes that regulate processes that occur inside heart muscle cells.

Researchers used ERRg activity in the human heart muscle cells and found reduced expression of several genes related to the heart. The heart cells showed irregular beating and prolonged contraction as well. The report added that researchers also found a key mechanism involved in pathophysiology of atrial fibrillation. 

The team used a statistical tool called polygenic risk score to predict someone’s genetic susceptibility to diseases. Also, new data from Japan showed that the higher the score the younger people were when they developed atrial fibrillation. It also showed the score was associated with a stroke.

“By applying our model to a person’s genome, we can find clinically undetectable heart arrhythmias or other related conditions,” Miyazawa said. “This is critical as finding those at risk before they have a stroke is the goal for any risk-prediction analysis. The new study also suggests potential targets for pharmaceutical intervention for those identified as at risk.”