Evidence map›Paper›PMID 42684112›Full record

ArticleHepatology communications2026

HLA and non-HLA genetic analyses reveal suggestive variants associated with statin-induced liver injury.

Callie Jo Zaborenko, Tae-Hwi Schwantes-An, Yi-Ju Li, Andrew Dellinger, Paola Nicoletti, Ann K Daly, Guruprasad Aithal, Naga Chalasani, Drug-Induced Liver Injury Network

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Article in Hepatology communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Callie Jo ZaborenkoDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Tae-Hwi Schwantes-AnDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Yi-Ju LiDepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA.
Andrew DellingerDuke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Paola NicolettiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ann K DalyTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Guruprasad AithalNIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals and the University of Nottingham, Nottingham, UK.
Naga ChalasaniDivision of Gastroenterology and Hepatology, Indiana University, School of Medicine, Indianapolis, Indiana, USA.
Drug-Induced Liver Injury Network

Funding

Coordinating Center for the Drug Induced Liver Injury Network (DILIN)U24DK065176 · NIDDK · DUKE UNIVERSITY · PI BARNHART, HUIMAN X · 2018 to 2022
$7.6M
IU Clinical Center: Drug Induced Liver Injury NetworkU01DK065211 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI NAGA P CHALASANI · 2003 to 2026
$7.5M
University of North Carolina Clinical Center for DILINU01DK065201 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PAUL B WATKINS · 2003 to 2026
$7.3M
Michigan Hepatotoxicity Clinical Research Network Renewal 2018U01DK065184 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROBERT J FONTANA · 2003 to 2026
$7.0M
The Drug Induced Liver Injury Network (DILIN): Focus on Herbal and DietarySupplementsU01DK083027 · NIDDK · THOMAS JEFFERSON UNIVERSITY · PI Dina Halegoua-DeMarzio · 2008 to 2026
$7.0M
USC-UCLA Drug-Induced Liver Injury (DILI) Clinical Center.U01DK083020 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Lily Dara · 2008 to 2026
$5.9M
NIDDK NIH HHS U01 DK065184NIDDK NIH HHS U01 DK065201NIDDK NIH HHS U01 DK065211NIDDK NIH HHS U01 DK083020NIDDK NIH HHS U01 DK083027NIDDK NIH HHS U24 DK065176
6 · The paper itself

Abstract

backgroundStatins are widely prescribed for cardiovascular risk reduction and are generally well tolerated. However, they can cause drug-induced liver injury (DILI), and the genetic factors contributing to statin-DILI remain poorly understood.

methodsHLA association and genome-wide association (GWAS) studies were conducted to identify genetic variants associated with statin-DILI. High-confidence cases (n=71) were identified from the Drug-Induced Liver Injury Network (DILIN) and compared with statin-exposed controls without liver injury (n=551) from the Indiana Biobank. Association testing was performed across ancestries and within ancestry, adjusting for age, sex, and three principal components of genotypes. Top variants were further evaluated in non-statin DILI cases and unexposed controls. In addition, we investigated the frequency of candidate variants among a comprehensive list of pharmacogenetic variants related to statins.

resultsHLA-DQA1*03:01 was significantly associated with increased risk of statin-DILI (OR=3.49, 95% CI 2.21-5.51, p-value=1.27×10-7), with enrichment observed across multiple ancestry groups, particularly non-Hispanic Black and Hispanic individuals. From the GWAS, three loci showed suggestive associations (p-value <5×10-06) with statin-DILI, including rs35197737 in RGS1 (OR=5.03, 95% CI 1.11-3.66, p=1.14×10-7), rs75629598 in FRMD4A (OR=4.4, 95% CI=2.33-8.12, p=3.97×10-6), and rs7658630 in the intergenic region on chromosome 4 (OR=4.86, 95% CI 2.66-8.85, p=2.68×10-7). No pharmacogenetic variants revealed statistical significance.

conclusionWe identified HLA and non-HLA genetic variants associated with statin DILI. Future studies with larger sample sizes should confirm these observations.

Indexed as

Chemical and Drug Induced Liver InjuryHLA AntigensHLA-DQ alpha-ChainsHydroxymethylglutaryl-CoA Reductase InhibitorsAgedCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideHLA AntigensHLA-DQA1 antigenHLA-DQ alpha-ChainsHydroxymethylglutaryl-CoA Reductase Inhibitorsdrugliver diseaseMASLDpharmacovigilancetoxicology

Identifiers

PMID42684112
PMCPMC13533501

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