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

doi:10.1038/ncomms10190

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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34 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 language	English
Article number	10190
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10190
Publication status	Published - Feb 2 2016
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms10190

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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, Article 10190. https://doi.org/10.1038/ncomms10190

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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.",

author = "Tsai, {Chia Ti} and Hsieh, {Chia Shan} and Chang, {Sheng Nan} and Chuang, {Eric Y.} and Ueng, {Kwo Chang} and Tsai, {Chin Feng} and Lin, {Tsung Hsien} and Wu, {Cho Kai} and Lee, {Jen Kuang} and Lin, {Lian Yu} and Wang, {Yi Chih} and Yu, {Chih Chieh} and Lai, {Ling Ping} and Tseng, {Chuen Den} and Hwang, {Juey Jen} and Chiang, {Fu Tien} and Lin, {Jiunn Lee}",

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AU - Tsai, Chia Ti

AU - Hsieh, Chia Shan

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AU - Chuang, Eric Y.

AU - Ueng, Kwo Chang

AU - Tsai, Chin Feng

AU - Lin, Tsung Hsien

AU - Wu, Cho Kai

AU - Lee, Jen Kuang

AU - Lin, Lian Yu

AU - Wang, Yi Chih

AU - Yu, Chih Chieh

AU - Lai, Ling Ping

AU - Tseng, Chuen Den

AU - Hwang, Juey Jen

AU - Chiang, Fu Tien

AU - Lin, Jiunn Lee

PY - 2016/2/2

Y1 - 2016/2/2

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

UN SDGs

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