Beyond single-slope Mendelian randomization: structural representation of genetic heterogeneity in joint effect space

Causal effects in complex traits are typically represented by a single linear slope. While conventional Mendelian randomization (MR) provides efficient scalar estimates, projection-based summaries do not explicitly capture structural organisation in joint effect space under genetic heterogeneity. We introduce MR-UBRA (Mendelian randomization-Unified Bayesian Risk Architecture), a probabilistic framework that decomposes instrumental variants into genetic risk fragments (GRFs) and quantifies extreme deviations using tail-risk metrics defined on the standardised residual magnitude |e|. MR-UBRA preserves the classical MR estimand while offering a structurally resolved representation of genetic heterogeneity. Across stroke subtypes, AF-CES, smoking-lung cancer, and BMI-T2D, effect-space distributions exhibit reproducible asymmetry, amplitude stratification, and multi-modal structure. MR-UBRA resolves component-level organisation, separating tail-dominant contributions from the causal core while maintaining consistency with the classical MR estimand. Simulations and boundary regimes demonstrate adaptive model complexity: MR-UBRA selects K>1 when multi-component structure is present and collapses to K=1 under homogeneous conditions, avoiding spurious stratification. These results support viewing causal effects in complex traits as structured distributions in joint effect space, enhancing causal representation without altering the MR estimand.