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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.

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