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, Jiunn Lee Lin

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13 Citations (Scopus)

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 x 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.

Original languageEnglish
Article number10190
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Feb 2 2016
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Tsai, C. T., Hsieh, C. S., Chang, S. N., Chuang, E. Y., Ueng, K. C., Tsai, C. F., Lin, T. H., Wu, C. K., Lee, J. K., Lin, L. Y., Wang, Y. C., Yu, C. C., Lai, L. P., Tseng, C. D., Hwang, J. J., Chiang, F. T., & Lin, J. L. (2016). Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation. Nature Communications, 7, [10190]. https://doi.org/10.1038/ncomms10190