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

PLoS Genetics
Oneil G BhalalaChristopher R Sibley

Abstract

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 CHRN...Continue Reading

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Citations

Oct 28, 2019·Autism Research : Official Journal of the International Society for Autism Research·Lu XiaFengyu Zhang
Aug 12, 2020·Genetic Epidemiology·Shrayashi BiswasSamsiddhi Bhattacharjee
Dec 6, 2018·Nature Reviews. Nephrology·Matthew G Sampson
Nov 3, 2020·Bioinformatics·Li LiuGreg Gibson

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Datasets Mentioned

BETA
AF131216

Methods Mentioned

BETA
genotyping

Software Mentioned

rAggr
Ensembl Variant Effect Predictor
Cross Disorder Analysis
R package qvalue
eCAVIAR
Coloc
Blood eQTL Browser
Matrix eQTL
R
CONVERGE

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