ArticleThe pharmacogenomics journal2016
A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.
Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in The pharmacogenomics journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02783469 (Genetics of Diabetes Audit and Research in Tayside Scotland), which is not on this map. Cited by 39 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 6% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetics of Diabetes Audit and Research in Tayside Scotland (DOLORisk Dundee)
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors.Pharmacogenetics and genomics · 2017Pooled it
- The Genetic Architecture of Chronic Cough: From Sensory Hypersensitivity to Treatable Trait.Pulmonary therapy · 2026Review
- Separating the genetics of disease, treatment, and treatment response using graphical modeling and large-scale electronic health records.medRxiv : the preprint server for health sciences · 2026Article
- Genomics of chronic dry cough unravels neurological pathways.The European respiratory journal · 2025Article
- A narrative review of research advancements in pharmacogenetics of cardiovascular disease and impact on clinical implications.NPJ genomic medicine · 2025Review
- Machine Learning Identifies Key Gene Markers Related to Fetal Retina Development at Single-Cell Transcription Level.Investigative ophthalmology & visual science · 2025Article
- Pharmacogenomic biomarkers of ACE inhibitor-induced cough in a multi-ethnic UAE cohort.Frontiers in pharmacology · 2025Article
- Using electronic health records for clinical pharmacology research: Challenges and considerations.Clinical and translational science · 2024Review
- Genome-wide association study identified six loci associated with adverse drug reactions to aripiprazole in schizophrenia patients.Schizophrenia (Heidelberg, Germany) · 2023Article
- Antihypertensives associated adverse events: a review of mechanisms and pharmacogenomic biomarkers available evidence in multi-ethnic populations.Frontiers in pharmacology · 2023Review
- Polygenic risk score for ACE-inhibitor-associated cough based on the discovery of new genetic loci.European heart journal · 2022Article
- Evaluating the frequency and the impact of pharmacogenetic alleles in an ancestrally diverse Biobank population.Journal of translational medicine · 2022Article
- Angiotensin-converting enzyme 1 and voltage-gated potassium channel-interacting protein 4 gene polymorphisms in COVID-19 patients from east of Iran.Clinica chimica acta; international journal of clinical chemistry · 2022Article
- Genome-wide association and genotype by environment interactions for growth traits in U.S. Red Angus cattle.BMC genomics · 2022Article
- WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care.The World Allergy Organization journal · 2022Review
- Genetic Variants Associated with Adverse Events after Angiotensin-Converting Enzyme Inhibitor Use: Replication after GWAS-Based Discovery.Yonsei medical journal · 2022Article
- Genome-Wide Approach to Measure Variant-Based Heritability of Drug Outcome Phenotypes.Clinical pharmacology and therapeutics · 2021Article
- Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.The pharmacogenomics journal · 2020Article
- Translational Informatics Connects Real-World Information to Knowledge in an Increasingly Data-Driven World.Clinical pharmacology and therapeutics · 2020Article
- Development of a System for Postmarketing Population Pharmacokinetic and Pharmacodynamic Studies Using Real-World Data From Electronic Health Records.Clinical pharmacology and therapeutics · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 16 institutions in 3 countries.
J D MosleyDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
C M ShafferDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
S L Van DriestDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
P E WeekeDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Q S WellsDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
J H KarnesDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
D R Velez EdwardsDepartment of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA.
W-Q WeiBiomedical Informatics, Vanderbilt University, Nashville, TN, USA.
P L TeixeiraBiomedical Informatics, Vanderbilt University, Nashville, TN, USA.
L BastaracheBiomedical Informatics, Vanderbilt University, Nashville, TN, USA.
D C CrawfordDepartment of Epidemiology and Biostatistics; Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
R LiDivision of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD, USA.
T A ManolioDivision of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD, USA.
E P BottingerCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
C A McCartyEssentia Institute of Rural Health, Duluth, MN, USA.
J G LinnemanMarshfield Clinic Research Foundation, Marshfield, WI, USA.
M H BrilliantMarshfield Clinic Research Foundation, Marshfield, WI, USA.
J A PachecoCenter for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
W ThompsonCenter for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
R L ChisholmCenter for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
G P JarvikDepartments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, WA, USA.
D R CrosslinDepartments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, WA, USA.
D S CarrellGroup Health Research Institute, Seattle, WA, USA.
E BaldwinGroup Health Research Institute, Seattle, WA, USA.
J RalstonGroup Health Research Institute, Seattle, WA, USA.
E B LarsonGroup Health Research Institute, Seattle, WA, USA.
J GraftonGroup Health Research Institute, Seattle, WA, USA.
A ScrolGroup Health Research Institute, Seattle, WA, USA.
H JouniDivision of Cardiovascular Diseases, Mayo Clinic, Rochester MN, USA.
I J KulloDivision of Cardiovascular Diseases, Mayo Clinic, Rochester MN, USA.
G TrompThe Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
K M BorthwickThe Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
H KuivaniemiThe Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
D J CareyThe Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA, USA.
M D RitchieDepartment of Biochemistry and Molecular Biology, Penn State University, University Park, PA, USA.
Y BradfordDepartment of Biochemistry and Molecular Biology, Penn State University, University Park, PA, USA.
S S VermaDepartment of Biochemistry and Molecular Biology, Penn State University, University Park, PA, USA.
C G ChuteSchools of Medicine, Public Health, and Nursing, Johns Hopkins University, Baltimore, MD, USA.
A VeluchamyMedical Research Institute, University of Dundee, Dundee, UK.
M K SiddiquiMedical Research Institute, University of Dundee, Dundee, UK.
C N A PalmerMedical Research Institute, University of Dundee, Dundee, UK.
A DoneyMedical Research Institute, University of Dundee, Dundee, UK.
S H MahmoudPourUtrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
A H Maitland-van der ZeeUtrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
A D MorrisSchool of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Edinburgh, UK.
J C DennyDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
D M RodenDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Vanderbilt University · USKaiser Permanente Washington Health Research Institute · USGeisinger Health System · USUniversity of Dundee · GBNorthwestern University · USPennsylvania State University · USMarshfield Clinic · USMayo Clinic in Arizona · USNational Human Genome Research Institute · USUniversity of Washington Medical Center · USUtrecht University · NLCase Western Reserve University · USEssentia Health · USIcahn School of Medicine at Mount Sinai · USJohns Hopkins University · USUniversity of Edinburgh · GB
Funding
Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8MThe Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4MFurthering scientific understanding of mechanisms underlying resilience to the effects of AD pathology by incorporating state of the art quantification of gliosis, inflammation, & synaptic toxicityU01AG006781 · NIA · UNIVERSITY OF WASHINGTON · PI CRANE, PAUL K, LARSON, ERIC B · 1986 to 2020
$39.3MInstitutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3MPharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4MResearch BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3MCLINICAL PHARMACOLOGY TRAINING PROGRAMT32GM007569 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Bjorn C Knollmann · 1985 to 2026
$12.4MVanderbilt Genome-Electronic Records ProjectU01HG004603 · NHGRI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2007 to 2011
$7.3MVESPA: Vanderbilt Electronic Systems for Pharmacogenomic AssessmentRC2GM092618 · NIGMS · VANDERBILT UNIVERSITY · PI DENNY, JOSHUA C., RODEN, DAN M · 2009 to 2010
$6.4MFrom GWAS to PheWAS: Scanning the EMR Phenome for Gene-disease AssociationsR01LM010685 · NLM · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BASTARACHE, LISA · 2011 to 2022
$6.3MVGER, the Vanderbilt Genome-Electronic Records ProjectU01HG008672 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DENNY, JOSHUA C., RODEN, DAN M · 2015 to 2019
$5.1MAmerican Heart Association-American Stroke Association 16FTF30130005NCATS NIH HHS UL1 TR000427NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001422NHGRI NIH HHS U01 HG004599NHGRI NIH HHS U01 HG004603NHGRI NIH HHS U01 HG004608NHGRI NIH HHS U01 HG004609NHGRI NIH HHS U01 HG006375NHGRI NIH HHS U01 HG006378NHGRI NIH HHS U01 HG006382NHGRI NIH HHS U01 HG006389NHGRI NIH HHS U01 HG008672NHGRI NIH HHS U01 HG008673NHLBI NIH HHS U19 HL065962NIA NIH HHS U01 AG006781NIDDK NIH HHS P30 DK072488NIDDK NIH HHS R01 DK088231NIDDK NIH HHS R01 DK091601NIGMS NIH HHS RC2 GM092618NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM007569NLM NIH HHS R01 LM010685Wellcome TrustWellcome Trust 084727/Z/08/ZWellcome Trust 085475/B/08/ZWellcome Trust 085475/Z/08/Z
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.
Indexed as
Polymorphism, Single NucleotideAngiotensin-Converting Enzyme InhibitorsCase-Control StudiesComputational BiologyCoughDatabases, GeneticElectronic Health RecordsFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansKv Channel-Interacting ProteinsLogistic ModelsMaleMultivariate AnalysisAngiotensin-Converting Enzyme InhibitorsKCNIP4 protein, humanKv Channel-Interacting Proteins
Identifiers
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Read underepoch 390
Registered trials
NCT02783469ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.