Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese population
Abstract 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 p...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-97794-7 |
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| author | Kanji Tabata Takeaki Sudo Yuki Nagata Kensuke Ihara Ken Asada Atsuhiro Kinoshita Yasuaki Tanaka Yasuteru Yamauchi Takeshi Sasaki Hitoshi Hachiya Yasushi Imai Hideo Fujita Tetsuo Sasano Tetsushi Furukawa Takanori Iwata Toshihiro Tanaka |
| author_facet | Kanji Tabata Takeaki Sudo Yuki Nagata Kensuke Ihara Ken Asada Atsuhiro Kinoshita Yasuaki Tanaka Yasuteru Yamauchi Takeshi Sasaki Hitoshi Hachiya Yasushi Imai Hideo Fujita Tetsuo Sasano Tetsushi Furukawa Takanori Iwata Toshihiro Tanaka |
| author_sort | Kanji Tabata |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-a02b51e1b215455b970fbe45ca03b3ab |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a02b51e1b215455b970fbe45ca03b3ab2025-08-20T03:18:41ZengNature PortfolioScientific Reports2045-23222025-04-0115111010.1038/s41598-025-97794-7Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese populationKanji Tabata0Takeaki Sudo1Yuki Nagata2Kensuke Ihara3Ken Asada4Atsuhiro Kinoshita5Yasuaki Tanaka6Yasuteru Yamauchi7Takeshi Sasaki8Hitoshi Hachiya9Yasushi Imai10Hideo Fujita11Tetsuo Sasano12Tetsushi Furukawa13Takanori Iwata14Toshihiro Tanaka15Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (Science Tokyo)Department of Educational Media Development, Institute of Science Tokyo (Science Tokyo)Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (Science Tokyo)Department of Bio-Informational Pharmacology, Medicine Research Institute, Institute of Science Tokyo (Science Tokyo)Cancer Translational Research Team, RIKEN Center for Advanced Intelligence ProjectDepartment of Educational Media Development, Institute of Science Tokyo (Science Tokyo)Department of Cardiology, Yokosuka Kyosai HospitalDepartment of Cardiology, Yokohama City Minato Red Cross HospitalDepartment of Cardiology, Heart Rhythm Center, National Hospital Organization Disaster Medical CenterCardiology Division, Cardiovascular Center, Tsuchiura Kyodo General HospitalDivision of Clinical Pharmacology, Department of Pharmacology, Jichi Medical UniversityDivision of Cardiovascular Medicine, Saitama Medical Center, Jichi Medical UniversityDepartment of Cardiovascular Medicine, Institute of Science Tokyo (Science Tokyo)Department of Bio-Informational Pharmacology, Medicine Research Institute, Institute of Science Tokyo (Science Tokyo)Department of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (Science Tokyo)Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (Science Tokyo)Abstract 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.https://doi.org/10.1038/s41598-025-97794-7Paroxysmal atrial fibrillationExome sequencingGene-based testsJapanese population |
| spellingShingle | Kanji Tabata Takeaki Sudo Yuki Nagata Kensuke Ihara Ken Asada Atsuhiro Kinoshita Yasuaki Tanaka Yasuteru Yamauchi Takeshi Sasaki Hitoshi Hachiya Yasushi Imai Hideo Fujita Tetsuo Sasano Tetsushi Furukawa Takanori Iwata Toshihiro Tanaka Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese population Scientific Reports Paroxysmal atrial fibrillation Exome sequencing Gene-based tests Japanese population |
| title | Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese population |
| title_full | Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese population |
| title_fullStr | Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese population |
| title_full_unstemmed | Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese population |
| title_short | Rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a Japanese population |
| title_sort | rare genetic variants involved in increased risk of paroxysmal atrial fibrillation in a japanese population |
| topic | Paroxysmal atrial fibrillation Exome sequencing Gene-based tests Japanese population |
| url | https://doi.org/10.1038/s41598-025-97794-7 |
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