The principal MR test of a causal effect was conducted using inverse-variance weighted (IVW) regression. This method is based on a regression of the exposure and the outcome which assumes the intercept is constrained to zero, and produces a causal estimate of the exposure-outcome association. Where there was no evidence of global horizontal pleiotropy (P ≥ 0.05) from the second analysis (see previous paragraph), a FDR adjusted67 P-value < 0.01 from the IVW test was required for evidence of a causal effect. Where there was evidence of global horizontal pleiotropy (P < 0.05) from the second analysis, additional evidence was also sought from the sensitivity tests (MR Egger test and the weighted median test). To ensure that a causal effect was not driven by a single variant a ‘leave one variant out’ IVW regression analysis was conducted with the least significant observed P-value used to assess whether significance was maintained. We tested the causal effect of depression on 24 other traits, and the causal effect of 9 other traits on depression.
