Abstract
Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results(1,2), and 1 in 50 experiences drug-induced liver injury(3). Since genomic variation contributes to other forms of drug-induced liver injury(4,5), we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P = 2.3 × 10(-8), odds ratio = 8.3, 95% confidence interval = 3.6-19.2). Analysis of an independent cohort of IFN-β-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P = 7.6 × 10(-5)) and alkaline phosphatase (P = 4.9 × 10(-4)). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use.