Brain Banks Spur New Frontiers in Neuropsychiatric Research and Strategies for Analysis and Validation

Abstract

Neuropsychiatric disorders affect hundreds of millions of patients and families worldwide. To decode the molecular framework of these diseases, many studies use human postmortem brain samples. These studies reveal brain-specific genetic and epigenetic patterns via high-throughput sequencing technologies. Identifying best practices for the collection of postmortem brain samples, analyzing such large amounts of sequencing data, and interpreting these results are critical to advance neuropsychiatry. We provide an overview of human brain banks worldwide, including progress in China, highlighting some well-known projects using human postmortem brain samples to understand molecular regulation in both normal brains and those with neuropsychiatric disorders. Finally, we discuss future research strategies, as well as state-of-the-art statistical and experimental methods that are drawn upon brain bank resources to improve our understanding of the agents of neuropsychiatric disorders.

Keywords: Brain bank; Expression quantitative trait loci; GWAS interpretation; Neuropsychiatric disorders; Postmortem brain.

Figure 1

Overview of the representative brain projects Numbers in cycles indicate the number of brain samples used in each project. Different data types are indicated using different colors, which include genotype, RNA expression, DNA methylation, and histone modification data. Colors in the bottom panel indicate the distribution of healthy controls or patients with different diseases included in the respective projects. The projects and their web links for access were listed below. BrainCloud (http://braincloud.jhmi.edu/) ; BrainSpan (http://www.brainspan.org/) , ; UKBEC, UK Brain Expression Consortium (www.braineac.org/) ; GTEx, Genotype Tissue Expression Project (https://gtexportal.org/) ; CMC, CommonMind Consortium (commonmind.org/) ; BrainSeq (http://eqtl.brainseq.org/) ; ROSMAP, the Religious Orders Study and Memory and Aging Project (http://www.radc.rush.edu/) . Only Capstone 1 data from PsychENCODE (http://www.psychencode.org/) were summarized in this figure. PsychENCODE Capstone 1 data comprise BrainGVEX, BrainSpan, CommonMind, UCLA- ASD, Yale- ASD, BipSeq, LIBD szControl, and CMC_HBCC datasets, but does not include fetal brain samples and outliers. CTL, control; SCZ, schizophrenia; MDD, major depressive disorder; BIP, bipolar disorder; AD, Alzheimer’s disease; ASD, autism spectrum disorder.

Figure 2

Overview of strategies and methods in neuropsychiatric studies