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Extensive sex differences in depression-linked variants functionally assayed in mouse brain

ABSTRACT: Extensive sex differences in depression-linked variants functionally assayed in mouse brain

PROVIDER: PRJNA773430 | ENA |

REPOSITORIES: ENA

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Extensive sex differences in depression-linked variants functionally assayed in mouse brain [Hippocampus]

Project description:Here, we selected >1000 variants from over 30 depression-associated loci using brain epigenomic data, and functionally assayed them using in vivo functional assays in the mouse brain to examine sex-by-genotype interactions. We identify extensive sex-by-allele effects in mature hippocampus, suggesting genetic risk and thus disease mechanisms may be distinct between the sexes. Unbiased informatics approaches indicated a role for nuclear hormone receptors, which was supported by . Further, comparative analysis of allelic function in the neonatal mouse brain, during a key between developmental neonates during the masculinizing testosterone surge, and in the adult hippocampus—a region of interest in depression pathology—but not at 10 days old, a older hormonally quiescent developmental stage juveniles. Our study provides novel insights into depression genetics as influenced by age, biological sex, and cell type, and provides a framework for in vivo parallel assays at a scale not previously shown possible to functionally define interactions between sex and disease variation.

2023-02-10 | GSE186346 | GEO

Extensive sex differences in depression-linked variants functionally assayed in mouse brain [P0&P10]

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Extensive sex differences in depression-linked variants functionally assayed in mouse brain [Hippocampus II]

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Extensive sex differences in depression-linked variants functionally assayed in mouse brain [Hippocampus]

Project description:Extensive sex differences in depression-linked variants functionally assayed in mouse brain [Hippocampus]

| PRJNA773474 | ENA

Extensive sex differences in depression-linked variants functionally assayed in mouse brain [P0&P10]

Project description:Extensive sex differences in depression-linked variants functionally assayed in mouse brain [P0&P10]

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Extensive sex differences in depression-linked variants functionally assayed in mouse brain [Hippocampus II]

Project description:Extensive sex differences in depression-linked variants functionally assayed in mouse brain [Hippocampus II]

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Extensive sex differences in depression-linked variants functionally assayed in mouse brain

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-10 | GSE186348 | GEO

Sex-specific Transcriptional Signatures in Human Depression

Project description:Sex-specific Transcriptional Signatures in Human Depression

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Sex-specific role for the long non-coding RNA linc00473 in depression

Project description:Depression is a common disorder that affects women at twice the rate of men. Here we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans, and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene, linc00473, as downregulated in prefrontal cortex of depressed females but not males. Using viral-mediated gene transfer to express linc00473 in mouse prefrontal cortex neurons, we mirrored the human sex-specific phenotype by inducing stress resilience solely in female mice. This sex-specific phenotype was accompanied by changes in synaptic function and gene expression selectively in female mice and, along with studies of human neuron-like cells in culture, implicates linc00473 as a CREB effector. Together, our studies identify linc00473 as a female-specific driver of stress resilience that is aberrant in female depression.

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Gene Expression Profiles Predict Postpartum-onset Depression Patients with Treatment-Resistant Depression Patients with Treatment-Resistant Depression

Project description:To identify early predictive biomarkers for postpartum depression using peripheral blood gene expression profiles

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