Chunk #2 — Results — Methylation quantitative trait loci (mQTL) in the developing human brain are widespread and predominantly characterized by cis effects
Despite the preponderance of cis-mQTLs, there are some notable trans-mQTL effects (Fig. 1c and Supplementary Table 4), consistent with previous reports of long-range genetic regulation of epigenetic variation in multiple cell-types19. Although the average effect size for trans-mQTLs is significantly lower than that observed for cis-mQTLs (two-sided Wilcoxon rank sum test, P = 6.74×10−7) (Supplementary Fig. 1), there is a higher proportion of larger (DNA methylation change per allele > 25%) effects among trans-mQTLs than cis-mQTLs (1.04% vs 0.715%). Of the 178 DNA methylation sites identified as being associated with trans-acting genetic variation in the fetal brain, 50 (28.09%) and 108 (60.67%) were also identified in studies of pancreatic islet cells16 and lymphocytes19, respectively (Supplementary Table 4 and Supplementary Table 5). These long-range associations between genotype and DNA methylation complement data showing interactions between regulatory elements spanning several Mb20, and even between chromosomes21.
