Systematically characterizing dysfunctional long intergenic non-coding RNAs in multiple brain regions of major psychosis

Abstract

Schizophrenia (SZ) and bipolar disorder (BD) are severe neuropsychiatric disorders with serious impact on patients, together termed “major psychosis”. Recently, long intergenic non-coding RNAs (lincRNAs) were reported to play important roles in mental diseases. However, little was known about their molecular mechanism in pathogenesis of SZ and BD. Here, we performed RNA sequencing on 82 post-mortem brain tissues from three brain regions (orbitofrontal cortex (BA11), anterior cingulate cortex (BA24) and dorsolateral prefrontal cortex (BA9)) of patients with SZ and BD and control subjects, generating over one billion reads. We characterized lincRNA transcriptome in the three brain regions and identified 20 differentially expressed lincRNAs (DELincRNAs) in BA11 for BD, 34 and 1 in BA24 and BA9 for SZ, respectively. Our results showed that these DELincRNAs exhibited brain region-specific patterns. Applying weighted gene co-expression network analysis, we revealed that DELincRNAs together with other genes can function as modules to perform different functions in different brain regions, such as immune system development in BA24 and oligodendrocyte differentiation in BA9. Additionally, we found that DNA methylation alteration could partly explain the dysregulation of lincRNAs, some of which could function as enhancers in the pathogenesis of major psychosis. Together, we performed systematical characterization of dysfunctional lincRNAs in multiple brain regions of major psychosis, which provided a valuable resource to understand their roles in SZ and BD pathology and helped to discover novel biomarkers.

WITHDRAWN: Exploring functions of long non-coding RNAs in HIV-associated neurocognitive disorder through weighted gene co-expression network analysis

“…In addition, H19 is associated with neural tube defects [19]. PRKCQ-AS1 has been reported to be involved in oligodendrocyte differentiation and CNS myelination [20]. ELOVL1 was demonstrated as a potential target in treatment of X-ALD (an inherited neurodegenerative disorder) [21].…”

Analysis of Gene Expression Variance in Schizophrenia Using Structural Equation Modeling

“…The difficulties in studying gene expression in human patients with neurological disease has led to the adoption of relevant cellular models (Evgrafov et al, 2006) to facilitate understanding of cellular phenotypes. While post-mortem brain tissue samples are used to study gene expression changes in neurological diseases like SCZ (e.g., Chen et al, 2013; Lanz et al, 2015; Hu et al, 2016), these are comprised of terminally differentiated neurons and glial cells of an adult brain which has been subjected to many different environmental conditions. Because SCZ can be considered a neurodevelopmental disorder (Weinberger, 1987; Raedler et al, 1998; Lewis and Levitt, 2002; Alexander-Bloch et al, 2014), the use of port-mortem samples may not necessarily accurately capture the alterations in neurodevelopmental processes important in SCZ, but rather the consequences of these changes in terminally-differentiated cells.…”

Quantifying RNA Editing in Deep Transcriptome Datasets

“…Editing dysregulation at recoding sites between two groups of samples is often assayed applying the twotailed MW U-test followed by Benjamin-Hochberg multiple test corrections. For example, such an approach was used to identify many recoding sites differentially edited in cancer compared with normal samples (Maas et al, 2001;Paz et al, 2007;Cenci et al, 2008;Chen et al, 2013;Qin et al, 2014;Han et al, 2015;Paz-Yaacov et al, 2015;Hu et al, 2016;Lin and Chen, 2019;Silvestris et al, 2019). Here, we demonstrate this approach by detecting statistically significant differentially recoded sites between 14 artery tibial and 12 cerebellum samples, looking at 1585 nonsynonymous REDIportal positions quantified using REDItools.…”