To ascertain the role of platelet glycoprotein Ib α-chain (GPIbα) plasma protein levels in cardiovascular, autoimmune, and autoinflammatory diseases and whether its effects are mediated by platelet count.
We performed a two-sample Mendelian randomization (MR) study, using both a cis-acting protein quantitative trait locus (cis-pQTL) and trans-pQTL near the GP1BA and BRAP genes as instruments. To assess if platelet count mediated the effect, we then performed a two-step MR study. Putative associations (GPIbα/platelet count/disease) detected by MR analyses were subsequently assessed using multiple-trait colocalization analyses.
After correction for multiple testing (Bonferroni-corrected threshold P ≤ 2 × 10
The role of platelets in thrombosis is well-established; however, our findings provide some novel genetic evidence that platelets may be causally implicated in the development of oligoarticular and RF-negative polyarticular JIA, and indicate that GPIbα may serve as a putative therapeutic target for these JIA subtypes.