A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.

Mosley JD, Shaffer CM, Van Driest SL, Weeke PE, Wells QS, Karnes JH, Velez Edwards DR, Wei WQ, Teixeira PL, Bastarache L, Crawford DC, Li R, Manolio TA, Bottinger EP, McCarty CA, Linneman JG, Brilliant MH, Pacheco JA, Thompson W, Chisholm RL, Jarvik GP, Crosslin DR, Carrell DS, Baldwin E, Ralston J, Larson EB, Grafton J, Scrol A, Jouni H, Kullo IJ, Tromp G, Borthwick KM, Kuivaniemi H, Carey DJ, Ritchie MD, Bradford Y, Verma SS, Chute CG, Veluchamy A, Siddiqui MK, Palmer CN, Doney A, MahmoudPour SH, Maitland-van der Zee AH, Morris AD, Denny JC, Roden DM
Pharmacogenomics J. 2016 16 (3): 231-7

PMID: 26169577 · PMCID: PMC4713364 · DOI:10.1038/tpj.2015.51

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.

MeSH Terms (22)

Angiotensin-Converting Enzyme Inhibitors Case-Control Studies Computational Biology Cough Databases, Genetic Electronic Health Records Female Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study Humans Kv Channel-Interacting Proteins Logistic Models Male Multivariate Analysis Odds Ratio Phenotype Polymorphism, Single Nucleotide Risk Assessment Risk Factors Scotland United States

Connections (4)

This publication is referenced by other Labnodes entities:

Links