Chunk #0 — Results — Methylation quantitative trait loci (mQTL) in the developing human brain are widespread and predominantly characterized by cis effects
We performed genome-wide single nucleotide polymorphism (SNP) genotyping and DNA methylation profiling in 166 human fetal brain samples ranging from 56 to 166 days post-conception (see Online Methods and Supplementary Table 1). After stringent quality-control we tested for an additive effect of allele dosage on DNA methylation across all potential pairings of 430,304 SNPs and 314,554 DNA methylation sites to identify fetal brain mQTLs (Supplementary Table 1). We identified 16,809 mQTLs at a conservative Bonferroni-corrected significance threshold of P < 3.69×10−13 (Supplementary Tables 2 and 3). The median DNA methylation change per allele across all identified mQTLs was 6.69% (interquartile range (IQR) = 3.17%–8.96%) for each mQTL SNP (Supplementary Fig. 1), slightly larger than reported in a previous analysis of genome-wide mQTLs in the adult brain (median effect size = 4.11%, IQR = 2.13–6.97%)7. The majority of mQTL SNPs (74.17%) are associated with DNA methylation at only a single probe; in contrast, most DNA methylation sites (69.83%) showing evidence for association do so with multiple mQTL SNPs, presumably as a result of linkage disequilibrium (LD) between SNPs (Supplementary Fig. 2). A searchable database of fetal brain mQTLs is available at: http://epigenetics.essex.ac.uk/mQTL/.
