CHIA-TI TSAIHsieh, Chia-ShanChia-ShanHsiehSHENG-NAN CHANGChuang, Eric YEric YChuangUeng, Kwo-ChangKwo-ChangUengTsai, Chin-FengChin-FengTsaiLin, Tsung-HsienTsung-HsienLinCHO-KAI WUJEN-KUANG LEELIAN-YU LINYI-CHIH WANGCHIH-CHIEH YULING-PING LAITseng, Chuen-DenChuen-DenTsengHWANG, JUEY-JENJUEY-JENHWANGFU-TIEN CHIANGJIUNN-LEE LINERIC YAO-YU CHUANG2022-09-202022-09-202016-02-022041-1723https://scholars.lib.ntu.edu.tw/handle/123456789/621205Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10(-24)). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway.enCALCIUM-CHANNEL; EXPRESSION; REPOLARIZATION; POPULATION; MYOCYTES; HEART; POLYMORPHISMS; ASSOCIATION; PHENOTYPES; CANDIDATE[SDGs]SDG3journal article10.1038/ncomms10190268313682-s2.0-84957535020WOS:000371138900001