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Increasing data have indicated familial clustering and participation of genetic factors in AVNRT, and no pathogenic genes related to AVNRT have been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing (WES) was performed in 82 patients with AVNRT and 100 controls. Reference genes, genome\u2010wide association analysis, gene\u2010based collapsing, and pathway enrichment analysis were performed. A protein\u2010protein interaction (PPI) network was then established; WES database in the UK Biobank and one only genetic study of AVNRT in Denmark were used for external data validation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 95 reference genes, 126 rare variants in 48 genes were identified in the cases (minor allele frequency\u00a0&lt;\u00a00.001). Gene\u2010based collapsing analysis and pathway enrichment analysis revealed six functional pathways related to AVNRT as with neuronal system\/neurotransmitter release cycles and ion channel\/cardiac conduction among the top 30 enriched pathways, and then 36 candidate pathogenic genes were selected. By combining with PPI analysis, 10 candidate genes were identified, including <jats:italic>RYR2, NOS1, SCN1A, CFTR<\/jats:italic>, <jats:italic>EPHB4, ROBO1, PRKAG2, MMP2, ASPH<\/jats:italic>, and <jats:italic>ABCC8<\/jats:italic>. From the UK Biobank database, 18 genes from candidate genes including <jats:italic>SCN1A, PRKAG2, NOS1<\/jats:italic>, and <jats:italic>CFTR<\/jats:italic> had rare variants in arrhythmias, and the rare variants in <jats:italic>PIK3CB, GAD2<\/jats:italic>, and <jats:italic>HIP1R<\/jats:italic> were in patients with PSVT. Moreover, one rare variant of <jats:italic>RYR2<\/jats:italic> (c.4652A\u00a0&gt;\u00a0G, p.Asn1551Ser) in our study was also detected in the Danish study. Considering the gene functional roles and external data validation, the most likely candidate genes were <jats:italic>SCN1A, PRKAG2, RYR2, CFTR<\/jats:italic>, <jats:italic>NOS1, PIK3CB, GAD2<\/jats:italic>, and <jats:italic>HIP1R<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The preliminary results first revealed potential candidate genes such as <jats:italic>SCN1A, PRKAG2, RYR2, CFTR<\/jats:italic>, <jats:italic>NOS1, PIK3CB, GAD2<\/jats:italic>, and <jats:italic>HIP1R<\/jats:italic>, and the pathways mediated by these genes, including neuronal system\/neurotransmitter release cycles or ion channels\/cardiac conduction, might be involved in AVNRT.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.25","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T15:02:38Z","timestamp":1591714958000},"page":"238-257","source":"Crossref","is-referenced-by-count":22,"title":["Identification of potential candidate genes and pathways in atrioventricular nodal reentry tachycardia by whole\u2010exome sequencing"],"prefix":"10.1002","volume":"10","author":[{"given":"Rong","family":"Luo","sequence":"first","affiliation":[{"name":"Institute of Geriatric Cardiovascular Disease Chengdu Medical College  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol School of Life Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuepin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shenzhen RealOmics (Biotech) Co., Ltd.  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