Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation.

Nature communications 2016

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Atrial 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.

Citation

Chia-Ti Tsai, Chia-Shan Hsieh, Sheng-Nan Chang, Eric Y Chuang, Kwo-Chang Ueng, Chin-Feng Tsai, Tsung-Hsien Lin, Cho-Kai Wu, Jen-Kuang Lee, Lian-Yu Lin, Yi-Chih Wang, Chih-Chieh Yu, Ling-Ping Lai, Chuen-Den Tseng, Juey-Jen Hwang, Fu-Tien Chiang, Jiunn-Lee Lin. Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation. Nature communications. 2016;7:10190