PUBLICATION
Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation
- Authors
- 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.
- ID
- ZDB-PUB-160203-7
- Date
- 2016
- Source
- Nature communications 7: 10190 (Journal)
- Registered Authors
- Keywords
- Biological sciences, Genetics
- MeSH Terms
-
- Animals
- Atrial Fibrillation/genetics*
- Cell Line
- Genome-Wide Association Study*
- Humans
- In Situ Hybridization
- Kv Channel-Interacting Proteins/genetics*
- Kv Channel-Interacting Proteins/metabolism*
- Mice
- Muscle Cells
- Myocytes, Cardiac/metabolism
- Zebrafish
- PubMed
- 26831368 Full text @ Nat. Commun.
Citation
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.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping