Genetic variability in the regulation of gene expression in ten regions of the human brain

Nat Neurosci. 2014 Oct;17(10):1418-1428. doi: 10.1038/nn.3801. Epub 2014 Aug 31.

Abstract

Germ-line genetic control of gene expression occurs via expression quantitative trait loci (eQTLs). We present a large, exon-specific eQTL data set covering ten human brain regions. We found that cis-eQTL signals (within 1 Mb of their target gene) were numerous, and many acted heterogeneously among regions and exons. Co-regulation analysis of shared eQTL signals produced well-defined modules of region-specific co-regulated genes, in contrast to standard coexpression analysis of the same samples. We report cis-eQTL signals for 23.1% of catalogued genome-wide association study hits for adult-onset neurological disorders. The data set is publicly available via public data repositories and via http://www.braineac.org/. Our study increases our understanding of the regulation of gene expression in the human brain and will be of value to others pursuing functional follow-up of disease-associated variants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / anatomy & histology*
  • Brain / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / pathology*
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Young Adult

Associated data

  • GEO/GSE46706
  • dbGaP/UNKNOWN