Neuroticism was the only trait with a putative causal effect on depression using the IVW regression analysis MR test (beta = 0.366, s.e = 0.037; PFDR = 2.63 × 10-21; Supplementary Figure 6). However, there was also evidence of variant heterogeneity (P = 9.62 × 10-21) requiring additional MR sensitivity testing. The weighted median test produced similar effect size and P-value to the IVW test (beta = 0.337, s.e. = 0.038; P = 1.94 × 10-18), but the MR Egger test had a large standard error and was in the opposite direction (beta = -0.128, s.e. = 0.271; P = 0.64). This putative causal effect remained consistent (P = 1.58 × 10-21) in the ‘leave one variant out’, IVW analysis indicating that the observed effect was not driven by a single variant.
