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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough
Pharmacogenomics Journal, Volume 16, No. 3, Year 2016
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Description
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. © 2016 Macmillan Publishers Limited.
Authors & Co-Authors
Mosley, Jonathan D.
United States, Nashville
Vanderbilt University
Shaffer, Christian M.
United States, Nashville
Vanderbilt University
Weeke, Peter Ejvin
United States, Nashville
Vanderbilt University
Denmark, Copenhagen
Københavns Universitet
Wells, Quinn Stanton
United States, Nashville
Vanderbilt University
Edwards, Digna R.Velez
United States, Nashville
Vanderbilt University
Bastarache, Lisa A.
United States, Nashville
Vanderbilt University
Crawford, Dana C.
United States, Cleveland
Case Western Reserve University
Li, Rongling
United States, Bethesda
National Human Genome Research Institute Nhgri
Manolio, Teri A.
United States, Bethesda
National Human Genome Research Institute Nhgri
Böttinger, Erwin P.
United States, New York
Icahn School of Medicine at Mount Sinai
McCarty, Catherine A.
Unknown Affiliation
Linneman, James G.
United States, Marshfield
Marshfield Clinic
Brilliant, Murray H.
United States, Marshfield
Marshfield Clinic
Pacheco, Jennifer A.
United States, Chicago
Northwestern University Feinberg School of Medicine
Thompson, William K.
United States, Chicago
Northwestern University Feinberg School of Medicine
Chisholm, Rex L.
United States, Chicago
Northwestern University Feinberg School of Medicine
Jarvik, Gail Pairitz
United States, Seattle
University of Washington
Crosslin, David R.
United States, Seattle
University of Washington
Carrell, David S.
United States, Seattle
Group Health Research Institute
Ralston, James D.
United States, Seattle
Group Health Research Institute
Larson, Eric B.
United States, Seattle
Group Health Research Institute
Grafton, Jane R.
United States, Seattle
Group Health Research Institute
Scrol, Aaron
United States, Seattle
Group Health Research Institute
Jouni, Hayan
United States, Rochester
Mayo Clinic
Kullo, Iftikhar J.
United States, Rochester
Mayo Clinic
Tromp, Gerard C.
United States
Geisinger Health System
Borthwick, Kenneth M.
United States
Geisinger Health System
Kuivaniemi, Helena
United States
Geisinger Health System
Carey, David J.
United States
Geisinger Health System
Ritchie, Marylyn D.
United States, University Park
Pennsylvania State University
Bradford, Yuki
United States, University Park
Pennsylvania State University
Verma, Shefali Setia
United States, University Park
Pennsylvania State University
Chute, Christopher G.
United States, Baltimore
Johns Hopkins University
Palmer, Colin Neil Alexander
United Kingdom, Dundee
University of Dundee
Doney, Alex S.F.
United Kingdom, Dundee
University of Dundee
Mahmoudpour, Seyed Hamidreza
Netherlands, Utrecht
Universiteit Utrecht
Maitland-Van der Zee, Anke H.
Netherlands, Utrecht
Universiteit Utrecht
Morris, Andrew D.
United Kingdom, Edinburgh
The University of Edinburgh
Denny, Joshua C.
United States, Nashville
Vanderbilt University
Roden, Dan M.L.
United States, Nashville
Vanderbilt University
Statistics
Citations: 41
Authors: 40
Affiliations: 16
Identifiers
Doi:
10.1038/tpj.2015.51
ISSN:
1470269X
Research Areas
Cancer
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study