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

研究成果: 雜誌貢獻 › 文章 › 同行評審

23 引文斯高帕斯（Scopus）

摘要

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.

原文	英語
文章編號	10190
期刊	Nature Communications
卷	7
DOIs	https://doi.org/10.1038/ncomms10190
出版狀態	已發佈 - 2月 2 2016
對外發佈	是

ASJC Scopus subject areas

化學 (全部)
生物化學、遺傳與分子生物學 (全部)
物理與天文學 (全部)

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此研究成果有助於以下永續發展目標

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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, [10190]. https://doi.org/10.1038/ncomms10190

@article{3c4e213202fd47fdaa54a07310b015ae,

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

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}",

note = "Funding Information: We thank all individuals in this study for their generous participation. This work was supported by grants from the National Taiwan University Hospital, Taipei, Taiwan (grant numbers 100CGN10, 100-S1650, UN102-052, 102-S2155,102-P04, 103-P05 and 103-P06), the Ministry of Science and Technology, R.O.C. (grant numbers 99-2314-B-002-118-MY3, 101-2314-B-002-181-MY3, 102-2628-B-002 -035 -MY3 and 104-2314-B-002-194-MY3) the New Century Health Care Promotion Foundation and the Clinical Trial and Research Center of the National Taiwan University Hospital, Taipei, Taiwan. We also thank the core laboratories of the Department of Medical Research in the National Taiwan University Hospital for technical assistance and for providing major core facilities. Publisher Copyright: {\textcopyright} 2016, Nature Publishing Group. All rights reserved.",

year = "2016",

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day = "2",

doi = "10.1038/ncomms10190",

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T1 - Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation

AU - Tsai, Chia Ti

AU - Hsieh, Chia Shan

AU - Chang, Sheng Nan

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

N1 - Funding Information: We thank all individuals in this study for their generous participation. This work was supported by grants from the National Taiwan University Hospital, Taipei, Taiwan (grant numbers 100CGN10, 100-S1650, UN102-052, 102-S2155,102-P04, 103-P05 and 103-P06), the Ministry of Science and Technology, R.O.C. (grant numbers 99-2314-B-002-118-MY3, 101-2314-B-002-181-MY3, 102-2628-B-002 -035 -MY3 and 104-2314-B-002-194-MY3) the New Century Health Care Promotion Foundation and the Clinical Trial and Research Center of the National Taiwan University Hospital, Taipei, Taiwan. We also thank the core laboratories of the Department of Medical Research in the National Taiwan University Hospital for technical assistance and for providing major core facilities. Publisher Copyright: © 2016, Nature Publishing Group. All rights reserved.

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

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