Yazdanpanah N, Yazdanpanah M, Wang Y, et al. - Applying an Mendelian randomization (MR) approach, three novel circulating protein biomarkers related to type 1 diabetes risk were unveiled in this study. Findings indicate the utility of these biomarkers as promising targets for development of drugs and/or of screening tools for early prediction of type 1 diabetes.

• In this large-scale two-sample MR study including 9,684 patients with type 1 diabetes and 15,743 controls, experts used cis genetic determinants (protein quantitative trait loci [pQTL]) of up to 1,611 circulating proteins from five large genome-wide association studies, to screen for causal links of these proteins with type 1 diabetes risk.

• Elevated risk of type 1 diabetes risk was observed in relation to a genetically predicted standard deviation (SD) increase in signal regulatory protein γ (SIRPG) level (MR odds ratio [OR] 1.66).

• Per genetically predicted SD increment in interleukin-27 Epstein-Barr virus–induced 3 (IL27-EBI3) protein levels was associated with an almost twofold increase in the risk of type 1 diabetes (MR OR 1.97).

• Reduced risk of type 1 diabetes was noted in relation to an SD increase in chymotrypsinogen B1 (CTRB1) (MR OR 0.84).

• Similar findings were obtained in sensitivity analyses using MR methods testing for pleiotropy while including trans-pQTL.