Chunk #7 — Results — Although the majority of fetal brain mQTLs are conserved in adult brain regions, there are fetal-specific genetic effects on DNA methylation at certain loci
even in mQTLs that do not meet our replication threshold (Supplementary Fig. 5). Of note, fetal brain mQTLs that do not replicate in adult brain are characterized by significantly lower effect sizes across all brain regions, including the fetal brain discovery sample (P = 3.18×10−141) (Supplementary Fig. 6). Despite the overall strong concordance in the direction of mQTL effects between fetal and adult brain, there are notable examples of heterogeneity between fetal and adult brain tissue. We used a multilevel linear regression model to test the significance of an interaction term and identify differential mQTL effects across our datasets. Of the 10,663 fetal mQTL effects tested, 3,173 (29.76%) were found to be significantly heterogeneous (Bonferroni-corrected P < 4.69 × 10−6) across the fetal and adult datasets (Supplementary Table 10). These include mQTLs that had notably larger or notably smaller effects in the adult brain, and fetal-specific mQTLs showing no significant association with DNA methylation in any adult brain region (see Fig. 2b). We also identified a small number (n = 45) of fetal brain mQTLs that had opposite effects on DNA methylation in fetal and adult brain samples (Fig. 2c and Supplementary Table 11).
