Supplementary material for "Deciphering the causal effects of circulating proteins on the risk of Graves' disease and Graves' ophthalmopathy".

It’s crucial to identify novel protein biomarkers and therapeutic targets for Graves' disease (GD) and Graves' ophthalmopathy (GO). Based on large-scale circulating proteomic data from the UK Biobank and deCODE, we conducted proteome-wide association analyses to identify causal plasma biomarkers for GD and GO. Combining BLISS and SMR analysis, we revealed 11 proteins associated with GD in European ancestry and 5 of them also related to GO. Besides, in the analysis aimed at East Asian ancestry, FCRL1, FCRL3, and CD40 were highlighted as consistent risk biomarkers across ancestries in the pathogenesis of GD. After colocalization and druggable validation, FCRL1 and CD40 were prioritized as protein targets for GD, while BRD2 and MICB similarly received high druggable evidence for GO. These findings offer novel insights into the etiology of GD and GO and highlight promising targets for screening biomarkers and developing therapeutic drugs.