Postmortem brain tissue as an underutilized resource to study the molecular pathology of neuropsychiatric disorders across different ethnic populations.

Neurosci Biobehav Rev

Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, 800 E. Leigh St., Biotech One, Suite 100, Richmond, VA 23219, USA; Department Psychiatry, Virginia Commonwealth University, 1200 East Broad Street, Richmond, VA 23298, USA; Center for Biomarker Research, Virginia Commonwealth University, Richmond, 410 North 12th Street, Richmond, VA 23298, USA; Department of Physiology & Biophysics, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA 23298, USA; Lieber Institute for Brain Development, Johns Hopkins University, 855 North Wolfe Street, Suite 300, 3rd Floor, Baltimore, MD 21205, USA. Electronic address:

Published: July 2019

AI Article Synopsis

  • Recent meta-analyses of genome-wide association studies have linked genetic variations to neuropsychiatric disorders like schizophrenia, bipolar disorder, and major depressive disorder, but most associated SNPs are found in non-coding regions of the genome.
  • There's a growing need to connect these genetic variants to gene expression in the brain, which is crucial for understanding these disorders, yet most existing postmortem brain samples primarily represent Caucasian individuals.
  • This review emphasizes the necessity of studying gene expression in diverse postmortem brain samples and proposes collaborations aimed at creating databases that include data from Chinese and other Asian populations to improve research outcomes.

Article Abstract

In recent years, large scale meta-analysis of genome-wide association studies (GWAS) have reliably identified genetic polymorphisms associated with neuropsychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD). However, the majority of disease-associated single nucleotide polymorphisms (SNPs) appear within functionally ambiguous non-coding genomic regions. Recently, increased emphasis has been placed on identifying the functional relevance of disease-associated variants via correlating risk polymorphisms with gene expression levels in etiologically relevant tissues. For neuropsychiatric disorders, the etiologically relevant tissue is brain, which requires robust postmortem sample sizes from varying genetic backgrounds. While small sample sizes are of decreasing concern, postmortem brain databases are composed almost exclusively of Caucasian samples, which significantly limits study design and result interpretation. In this review, we highlight the importance of gene expression and expression quantitative loci (eQTL) studies in clinically relevant postmortem tissue while addressing the current limitations of existing postmortem brain databases. Finally, we introduce future collaborations to develop postmortem brain databases for neuropsychiatric disorders from Chinese and Asian subpopulations.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643003PMC
http://dx.doi.org/10.1016/j.neubiorev.2019.04.015DOI Listing

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