New insight into the causal relationship between Graves' disease liability and drug eruption: a Mendelian randomization study

Abstract

Background: Graves' disease (GD) and drug eruption are closely associated and frequently observed in the clinical setting. However, it remains unclear whether a causal relationship exists between these two conditions. The aim of the study is to investigate whether GD is causal to drug eruptions using two-sample Mendelian randomization.

Methods: We launched a two-sample MR to investigate whether GD is causal to drug eruption using Genome-wide association study (GWAS) summary data from Biobank Japan and FinnGen. Genetic variants were used as instrumental variables to avoid confounding bias. Statistical methods including inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO were conducted to identify the robustness of the causal effect.

Results: Genetically predicted GD may increase the risk of drug eruption by 30.3% (OR=1.303, 95% CI 1.119-1.516, p<0.001) in the Asian population. In European populations, GD may increase the generalized drug eruption by 15.9% (OR=1.159, 95%CI 0.982-1.367, p=0.080).

Conclusions: We found GD is potentially causal to drug eruption. This finding expanded the view of the frequently observed co-existence of GD and adverse drug reactions involving the skin. The mechanism remains for further investigation.

Keywords: Asian population; European population; Graves’ disease; Mendelian randomization study; drug eruption.