DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Cough in response to angiotensin-converting enzyme inhibitor drugs. The EFO term response to angiotensin-converting enzyme inhibitor, Cough was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: response to angiotensin-converting enzyme inhibitor, Cough

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

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

TITLE:

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

JOURNAL:

The pharmacogenomics journal 06 2016, Vol 16, pp. 231-7

ABSTRACT:

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. PUBMED: 26169577
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