Identification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue

UK Brain Expression Consortium

Research output: Contribution to journalArticlepeer-review


Schizophrenia and the affective disorders, here comprising bipolar disorder and major depressive disorder, are psychiatric illnesses that lead to significant morbidity and mortality worldwide. Whilst understanding of their pathobiology remains limited, large case-control studies have recently identified single nucleotide polymorphisms (SNPs) associated with these disorders. However, discerning the functional effects of these SNPs has been difficult as the associated causal genes are unknown. Here we evaluated whether schizophrenia and affective disorder associated-SNPs are correlated with gene expression within human brain tissue. Specifically, to identify expression quantitative trait loci (eQTLs), we leveraged disorder-associated SNPs identified from 11 genome-wide association studies with gene expression levels in post-mortem, neurologically-normal tissue from two independent human brain tissue expression datasets (UK Brain Expression Consortium (UKBEC) and Genotype-Tissue Expression (GTEx)). Utilizing stringent multi-region meta-analyses, we identified 2,224 cis-eQTLs associated with expression of 40 genes, including 11 non-coding RNAs. One cis-eQTL, rs16969968, results in a functionally disruptive missense mutation in CHRNA5, a schizophrenia-implicated gene. Importantly, comparing across tissues, we find that blood eQTLs capture < 10% of brain cis-eQTLs. Contrastingly, > 30% of brain-associated eQTLs are significant in tibial nerve. This study identifies putatively causal genes whose expression in region-specific tissue may contribute to the risk of schizophrenia and affective disorders.

Original languageEnglish
Pages (from-to)e1007607
JournalPLoS Genetics
Issue number8
Publication statusPublished - 24 Aug 2018


  • Brain/metabolism
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Mood Disorders/diagnosis
  • Nerve Tissue Proteins/genetics
  • Polymorphism, Single Nucleotide
  • Principal Component Analysis
  • Quantitative Trait Loci
  • Receptors, Nicotinic/genetics
  • Schizophrenia/diagnosis


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