The genome-wide risk alleles for psychiatric disorders at 3p21.1 show convergent effects on mRNA expression, cognitive function, and mushroom dendritic spine

Yang, Zhihui; Zhou, Danyang; Li, Huijuan; Cai, Xin; Liu, Weipeng; Wang, Lu; Chang, Hong; Li, Ming; Xiao, Xiao

doi:10.1038/s41380-019-0592-0

Cited by 64 publications

(53 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fortunately, accumulating studies have found that noncoding variations of complex diseases tend to be associated with mRNA expression 7 , and analyzing the expression quantitative trait loci (eQTL) effects of the risk alleles in relevant tissues is therefore a plausible strategy to probe the risk genes from risk locus [8][9][10] . In line with this, several integrative analyses using GWAS and brain eQTL data have revealed susceptibility genes and potential biological mechanisms for psychiatric disorders [11][12][13] .…”

Section: Introductionmentioning

confidence: 77%

Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data

et al. 2020

Transl Psychiatry

Self Cite

View full text Add to dashboard Cite

Genome-wide association studies (GWAS) of major depression and its relevant biological phenotypes have been extensively conducted in large samples, and transcriptome-wide analyses in the tissues of brain regions relevant to pathogenesis of depression, e.g., dorsolateral prefrontal cortex (DLPFC), have also been widely performed recently. Integrating these multi-omics data will enable unveiling of depression risk genes and even underlying pathological mechanisms. Here, we employ summary data-based Mendelian randomization (SMR) and integrative risk gene selector (iRIGS) approaches to integrate multi-omics data from GWAS, DLPFC expression quantitative trait loci (eQTL) analyses and enhancer-promoter physical link studies to prioritize high-confidence risk genes for depression, followed by independent replications across distinct populations. These integrative analyses identify multiple high-confidence depression risk genes, and numerous lines of evidence supporting pivotal roles of the netrin 1 receptor (DCC) gene in this illness across different populations. Our subsequent explorative analyses further suggest that DCC significantly predicts neuroticism, well-being spectrum, cognitive function and putamen structure in general populations. Gene expression correlation and pathway analyses in DLPFC further show that DCC potentially participates in the biological processes and pathways underlying synaptic plasticity, axon guidance, circadian entrainment, as well as learning and long-term potentiation. These results are in agreement with the recent findings of this gene in neurodevelopment and psychiatric disorders, and we thus further confirm that DCC is an important susceptibility gene for depression, and might be a potential target for new antidepressants.

show abstract

Section: Introductionmentioning

confidence: 77%

Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data

et al. 2020

Transl Psychiatry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Studies in humans and animal models have revealed aberrations in dendritic spine architecture in several psychiatric disorders including depression and others related to stress (Edfawy et al, 2019;Guo et al, 2019;Yang et al, 2020). Changes in spine density and organization are thought to contribute to the behavioral disorder caused by stress exposure (Chen et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats

Lei

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

Prenatal stress (PS) can lead to neuroendocrine and emotional disorders later in adolescence. Sexual dimorphism in these neurodevelopmental outcomes have been observed; however, the underlying mechanisms are not fully understood. To address this issue, we investigated whether there are sex differences in epigenetic reprogramming in rats exposed to PS. Pregnant female rats were subjected to chronic restraint stress from gestational day (G)12 to G18. From postnatal day (P)38 to P45, subgroups of offspring including both males and females were subjected to behavioral testing and brain tissue specimens were analyzed by DNA pyrosequencing, western blotting, and Golgi staining to assess changes in methylation pattern of glucocorticoid receptor (GR) gene, expression of DNA methyltransferase (DNMT) and DNA demethylase, and dendrite morphology, respectively. The DNA methyltransferase inhibitor decitabine was administered to rats prior to PS to further evaluate the role of methylation in the sexually dimorphic effects of PS. The results showed that PS increased anxiety-like behavior in offspring, especially in females, while depression-like behavior was increased in male offspring compared to control littermates. The methylation pattern in the promoter region of the GR gene differed between males and females. Sex-specific changes in the expression of DNMTs (DNMT1 and DNMT3a) and DNA demethylase (Tet methylcytosine dioxygenase 2) were also observed. Interestingly, decitabine alleviated the behavioral disorder caused by PS and restored dendrite density and morphology in female but not male rats. These findings suggest that different change patterns of DNMT and demethylase in the two sexes after PS are responsible for the sexually dimorphism, which could have implications for the clinical management of stress-related disorders.

show abstract

“…Cortical neurons were prepared from E18 embryos of Sprague-Dawley rats, and cultured in serum-free medium following our previous studies [47,48]. Briefly, the frontal cortex tissues were dissected and minced in ice-cold sterile Hank's balanced salt solution.…”

Section: Rat Cortical Neuronal Culturesmentioning

confidence: 99%

“…Analysis of dendritic spines in cultured neurons was performed following previous studies [47,53]. Adamtsl3-shRNA, control shRNA, pCAG-control or pCAG-Ppp2r2b was respectively transfected into cortical neurons together with Venus plasmid (which expressed EGFP) using Lipofectamine 2000 (Invitrogen) at 14-15 DIV.…”

Section: Transfection In Rat Neurons and Quantitative Morphological Amentioning

confidence: 99%

Whole genome analyses reveal significant convergence in obsessive-compulsive disorder between humans and dogs

et al. 2021

Self Cite

View full text Add to dashboard Cite

The genome-wide risk alleles for psychiatric disorders at 3p21.1 show convergent effects on mRNA expression, cognitive function, and mushroom dendritic spine

Cited by 64 publications

References 132 publications

Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data

Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data

Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats

Whole genome analyses reveal significant convergence in obsessive-compulsive disorder between humans and dogs

Contact Info

Product

Resources

About