each test (n = 28; online Supplemental Table S1). Of the 17 MR tests conducted, we observed that 14 survived multiple testing correction (Table 1). This outcome was expected due to the strong genetic correlations observed among the traits investigated. To verify that the significant results were not due to the presence of biases in the genetic instruments, we conducted three main sensitivity analyses: (i) inspected consistency of direction of effects across MR methods (online Supplemental Table S5); (ii) tests of horizontal pleiotropy between the exposure and the outcome (MR-Egger regression intercept P > 0.1; online Supplemental Table S6); (iii) assessed heterogeneity of effect sizes among the variants included in the genetic instrument (heterogeneity test P > 0.05; online Supplemental Table S3). Of 14 MR tests surviving Bonferroni multiple testing correction, only the causal relationship of MD on AD passed all three sensitivity analyses. We observed that the MD instrumental variable based on suggestive variants (259 SNPs) was associated with AD (fixed-effect inverse-variance weighted method: β = 0.28, P = 1.3 × 10−6; Fig. 2). Since this causal estimate was generated from a genetic instrument including suggestive variants, we confirmed this result using the MR-RAPS method: β = 0.28, P
