An xQTL map integrates the genetic architecture of the human brain’s transcriptome and epigenome

We report a novel multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation, and histone acetylation data from the dorsolateral prefrontal cortex of 411 older adult individuals that have all three data types. We identify SNPs significantly associated with gene expression, DNA methylation, and histone modification levels. Many of these SNPs influence multiple molecular features, and we demonstrate that SNP effects on RNA expression are fully mediated by epigenetic features in 9% of these loci. Further, we illustrate the utility of our new resource, xQTL Serve, by using it to prioritize the cell type(s) most affected by an xQTL. We also re-analyze published genome wide association studies (GWAS) using a xQTL-weighted analysis approach and identify 18 new schizophrenia and 2 new bipolar susceptibility variants, which is more than double the number of loci that can be discovered with a larger blood-based eQTL resource.