Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese population

• Published in: Scientific reports Vol. 15; no. 1; pp. 13216 - 10
• Main Authors: Tabata, Kanji, Sudo, Takeaki, Nagata, Yuki, Ihara, Kensuke, Asada, Ken, Kinoshita, Atsuhiro, Tanaka, Yasuaki, Yamauchi, Yasuteru, Sasaki, Takeshi, Hachiya, Hitoshi, Imai, Yasushi, Fujita, Hideo, Sasano, Tetsuo, Furukawa, Tetsushi, Iwata, Takanori, Tanaka, Toshihiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.04.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 692/4019; 692/499; 692/699; Aged; Arrhythmia; Atrial Fibrillation - epidemiology; Atrial Fibrillation - genetics; Cardiac arrhythmia; Case-Control Studies; Congestive heart failure; East Asian People - genetics; Exome Sequencing; Female; Fibrillation; Gene-based tests; Genetic diversity; Genetic factors; Genetic Predisposition to Disease; Genetic variance; Genetic Variation; Genomic analysis; Humanities and Social Sciences; Humans; Japan - epidemiology; Japanese population; Male; Middle Aged; multidisciplinary; Paroxysmal atrial fibrillation; Pathogenesis; Polymorphism, Single Nucleotide; Risk Factors; Science; Science (multidisciplinary); Whole genome sequencing; Japan; Gene-based tests; Paroxysmal atrial fibrillation; Japanese population; Exome sequencing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-97794-7

Atrial fibrillation (AF) is the most prevalent arrhythmia in the world and can cause serious complications such as stroke or heart failure. Paroxysmal atrial fibrillation (PAF), a subtype of AF, accounts for approximately 25% of AF cases and is estimated to affect approximately 30 million people worldwide. Despite extensive genetic research on AF, the genetic factors involved in PAF in East Asian (EAS) populations remain unidentified. The aim of our study was to identify genetic factors associated with PAF in the Japanese population, contributing to our understanding of the genetic architecture of AF in Japanese populations. We conducted whole-exome sequencing on a cohort of 1176 PAF individuals and 1172 non-PAF control subjects in a Japanese population. We processed the sequencing data in accordance with the best practices outlined in the Genome Analysis Toolkit (GATK) and conducted gene-based association tests under three variant grouping strategies (masks) using the burden test, SKAT, and SKAT-O. We then performed a meta-analysis of the resulting P -values, which revealed that four genes— ZNF785 , SMPD3 , GFRA4 , and LGALS1 —were significantly associated with PAF, representing novel findings. These findings provide new insights into PAF pathogenesis and suggest potential biomarkers for early detection.