Phenome-Wide Screening Identified Novel Repurposing Potential for Paracetamol and Levothyroxine in Mental Health and Diabetes
Abstract
The availability of publicly available genetic data has the potential to accelerate medication repurposing efforts. In this study by integrating GWAS summary statistics for medication use with phenome data, Mendelian randomization and genetic correlation analyses were performed to find significant medication-trait associations. Genetic predisposition to paracetamol use was associated with a cluster of affective traits and alcohol intake. Examination of eQTL data revealed genes at 17q21 regions have pleiotropic effects on both paracetamol use and the identified traits. A second signal was identified between levothyroxine use and diabetes. Subjects that were genetically predisposed to use levothyroxine were at higher risk to develop diabetes. Conditional analysis indicates the use of levothyroxine will likely lower the risk of diabetes by lowering body weight. Findings from eQTL analysis identified several genes at HLA regions that exert pleiotropic effect on both traits.Our findings suggest that paracetamol warrants further investigation for the treatment of affective disorders and alcoholism, while levothyroxine may offer protective benefits against diabetes via weight modulation.
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