Mendelian randomization reveals the associations between modifiable risk factors and intermediate phenotypes and spontaneous abortion

The preliminary two-sample MR findings suggest immune signals (e.g., monocyte-related phenotypes) and highlight lifestyle correlates as potential priorities. Genetic instruments within the extended MHC region were associated with spontaneous abortion; however, given dense linkage disequilibrium across the locus, these signals are best interpreted as MHC-region associations rather than HLA-DR-specific effects. These results also require triangulation with complementary approaches-including polygenic risk score (PRS) analyses and prospective epidemiologic studies-before any causal interpretation or prevention guidance can be established.