TMPRSS5 and Stroke: As cis-pQTLs were considered to have a more direct and specific biological effect on the protein (compared to trans-pQTLs)24, we first performed MR analyses using only cis-pQTLs as instrumental variables and identified six putatively causal proteins with at least one stroke outcome (P ≤ 1.62 × 10−4 = 0.05/308 proteins; Figs. 2, 3 and Supplementary Fig. 1): TFPI (tissue factor pathway inhibitor), TMPRSS5 (Transmembrane Serine Protease 5), CD40 (B Cell Surface Antigen CD40), MMP12 (Matrix Metallopeptidase 12), IL6RA (Interleukin 6 Receptor) and CD6 (T-Cell Differentiation Antigen CD6).