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Chunk #28 — Online Methods — Identifying overlap and testing for enrichment of expression QTLs (eQTLs) among fetal brain mQTLs

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Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci.
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Prior to testing for a significant overlap with SNPs associated with brain eQTLs all SNPs associated with at least one DNA methylation site in the fetal brain were ‘clumped’ based on their best mQTL P-value using PLINK31 to create a list of quasi-independent SNPs (r2 < 0.25 for all pairs of SNPs within 250kb) and prevent LD between SNPs in the set biasing the results. Given the extensive correlation between variants in the major histocompatibility complex (MHC) region, a more stringent clumping procedure was used for SNPs located in chr6:25000000–35000000, where the window for pairwise SNP comparisons was extended to 10000kb. To test for a larger overlap than expected by chance, up to 1 million simulated sets, matched for allele frequency, were drawn to calculate the expected overlap and generate empirical P-values. SNPs were categorised into MAF bins split at intervals of 2%, and SNPs from each bin were selected to match the distribution in the test set. Empirical significance for enrichment of eQTLs in mQTLs was ascertained by counting the number of simulations with at least as many SNPs