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

Nat Neurosci
Authors
Keywords
Abstract

We report a 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 adults who 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 reanalyze published genome wide association studies using an 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 expression eQTL resource.

Year of Publication
2017
Journal
Nat Neurosci
Volume
20
Issue
10
Pages
1418-1426
Date Published
2017 Oct
ISSN
1546-1726
DOI
10.1038/nn.4632
PubMed ID
28869584
PubMed Central ID
PMC5785926
Links
Grant list
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
RF1 AG036042 / AG / NIA NIH HHS / United States