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

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 () and Jiunn-Lee Lin ()
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Chia-Ti Tsai: National Taiwan University College of Medicine and Hospital
Chia-Shan Hsieh: Genome and Systems Biology Degree Program, National Taiwan University
Sheng-Nan Chang: Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
Eric Y. Chuang: Genome and Systems Biology Degree Program, National Taiwan University
Kwo-Chang Ueng: School of Medicine, Chung Shan Medical University
Chin-Feng Tsai: School of Medicine, Chung Shan Medical University
Tsung-Hsien Lin: Kaohsiung Medical University and Chung-Ho Memorial Hospital
Cho-Kai Wu: National Taiwan University College of Medicine and Hospital
Jen-Kuang Lee: National Taiwan University College of Medicine and Hospital
Lian-Yu Lin: National Taiwan University College of Medicine and Hospital
Yi-Chih Wang: National Taiwan University College of Medicine and Hospital
Chih-Chieh Yu: National Taiwan University College of Medicine and Hospital
Ling-Ping Lai: National Taiwan University College of Medicine and Hospital
Chuen-Den Tseng: National Taiwan University College of Medicine and Hospital
Juey-Jen Hwang: National Taiwan University College of Medicine and Hospital
Fu-Tien Chiang: National Taiwan University College of Medicine and Hospital
Jiunn-Lee Lin: National Taiwan University College of Medicine and Hospital

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms10190

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