Using MR analysis for MS29, we identified 121 instruments (cis-eQTL SNPs) in 99 genes that passed the Bonferroni-adjusted P-value threshold of 1.43 × 10−7 (Supplementary Table 12); 25 of these instruments passed co-localization (Table 1 and Fig. 5b), of which 13 genes had a positive Wald ratio—indicating that increased gene expression increases disease risk—and the remainder a negative Wald ratio, indicating the opposite. A systematic comparison of the Wald ratio estimates on the 7,748 shared cis-eQTL genes between Cortex-EUR and eQTLGen14 (which instrumented the same genes but potentially with different SNPs) showed opposite effect directions for 3,173 (41.0%) genes (Supplementary Note, Supplementary Figs. 23,24 and Supplementary Table 14a). Although the agreement improved when the same SNP instrument was compared between studies, 2,671 (27.5%) of 9,728 MetaBrain Wald ratios still showed opposite directionality to eQTLGen (Supplementary Table 14b), underscoring the importance of tissue-specific differences when interpreting transcriptomics data.
