Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

Sci Data. 2020 Oct 12;7(1):340. doi: 10.1038/s41597-020-00642-8.

Abstract

The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975).

Publication types

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

MeSH terms

  • Cerebellar Cortex / metabolism*
  • Cerebral Cortex / metabolism*
  • Datasets as Topic
  • Gene Expression Profiling*
  • Genome-Wide Association Study
  • Humans
  • Meta-Analysis as Topic
  • Quantitative Trait Loci*
  • RNA, Long Noncoding / genetics
  • Schizophrenia / genetics

Substances

  • RNA, Long Noncoding

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