학술논문
A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough
Document Type
Academic Journal
Author
Mosley, J D; Shaffer, C M; Van Driest, S L; Weeke, P E; Wells, Q S; Karnes, J H; Edwards, Velez; Wei, W-Q; Teixeira, P L; Bastarache, L; Crawford, D C; Li, R; Manolio, T A; Bottinger, E P; McCarty, C A; Linneman, J G; Brilliant, M H; Pacheco, J A; Thompson, W; Chisholm, R L; Jarvik, G P; Crosslin, D R; Carrell, D S; Baldwin, E; Ralston, J; Larson, E B; Grafton, J; Scrol, A; Jouni, H; Kullo, I J; Tromp, G; Borthwick, K M; Kuivaniemi, H; Carey, D J; Ritchie, M D; Bradford, Y; Verma, S S; Chute, C G; Veluchamy, A; Siddiqui, M K; Palmer, C NA; Doney, A; MahmoudPour, S H; Maitland-van der Zee, A H; Morris, A D; Denny, J C; Roden, D M
Source
The Pharmacogenomics Journal. Jun 01, 2016 16(3):231-237
Subject
Language
English
ISSN
1470-269X
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). 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). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.