Polygenic architecture informs potential vulnerability to drug-induced liver injury.

ABSTRACT: Drug-induced liver injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market; this is partially due to the inability to identify patients who are at risk¹. In this study, we developed a polygenic risk score (PRS) for DILI by aggregating effects of numerous genome-wide loci identified from previous large-scale genome-wide association studies². The PRS predicted the susceptibility to DILI in patients treated with fasiglifam, amoxicillin-clavulanate or flucloxacillin and in primary hepatocytes and stem cell-derived organoids from multiple donors treated with over ten different drugs. Pathway analysis highlighted processes previously implicated in DILI, including unfolded protein responses and oxidative stress. In si

SUBMITTER: Koido M 

PROVIDER: S-EPMC8482794 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature