We also performed the SMR analysis to detect associations between DNAm sites and the brain-related phenotypes16 using brain mQTL data from Jaffe et al. (n = 526) and blood cis-mQTL data from a meta-analysis of LBC and BSGS (n = 1980) (Methods). We only included in the analysis DNAm probes with at least one cis-mQTL with PmQTL < 5 × 10−8 in both the brain and blood data sets. We identified 167 DNAm sites associated with the traits (PSMR < 1.8 × 10−6) using the brain mQTL data, 133 of which (79.6%) were in common with the set of 295 DNAm sites identified using the blood mQTL data (Fig. 5d and Supplementary Fig. 24). The brain to blood “replication” rate slightly decreased when we rejected the associations with PHEIDI < 0.05 (Supplementary Fig. 25), likely because of the HEIDI test being over-conservative especially as sample size increases21. These results further demonstrate the feasibility and gain of power of using the cis-genetic effects on gene expression or DNAm estimated in blood to identify putative target genes and regulatory DNA elements for brain-related phenotypes.
