Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood

Nat Commun. 2018 Jun 11;9(1):2282. doi: 10.1038/s41467-018-04558-1.


Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples ([Formula: see text] for cis-eQTLs and [Formula: see text] for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes.

Publication types

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

MeSH terms

  • Brain / metabolism*
  • DNA / blood*
  • DNA / genetics*
  • DNA Methylation
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Genetic Markers
  • Genome-Wide Association Study
  • Humans
  • Phenotype
  • Promoter Regions, Genetic
  • Quantitative Trait Loci*
  • Tissue Distribution
  • Transcriptome


  • Genetic Markers
  • DNA