Sa75large-Scale Transcriptome-Wide Characterization of Asd, Schizophrenia, and Bipolar Disorder

Gandal, Michael J.; Zhang, Pan; Walker, Rebecca L.; Won, Hyejung; Hadjimichael, Evi; Bakel, Harm van; Haney, Jillian R.; Jaffe, Andrew E.; White, Kevin P.; Peters, Mette A.; Gerstein, Mark; Liu, Chunyu; Iakoucheva, Lilia M.; Pinto, Dalila; Geschwind, Daniel H.

doi:10.1016/j.euroneuro.2018.08.297

Cited by 44 publications

(23 citation statements)

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“…Recently, the specific roles of the immune system in psychiatric diseases began to be revealed (Chen et al, 2016b;de Baumont et al, 2015;Dong et al, 2018b;Madore et al, 2016;Yuan et al, 2019). Particularly, neuroglial cells have gained importance as key neuroimmune players in the development of autism (microglia and oligodendrocytes [Scuderi and Verkhratsky, 2020], Alzheimer disease (microglia [Clayton et al, 2017], and schizophrenia (astrocytes [Gandal et al, 2018]. The association of pathways related to apoptosis, senescence, and cell differentiation with psychiatric disorders has also occurred recently, except with Alzheimer disease, which began early in the period (Figure 6).…”

Section: Evolution Of Biological Pathwaysmentioning

confidence: 99%

The evolution of knowledge on genes associated with human diseases

et al. 2022

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Section: Evolution Of Biological Pathwaysmentioning

confidence: 99%

The evolution of knowledge on genes associated with human diseases

et al. 2022

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“…We further annotated proximal candidate genes at risk loci using gene sets related to autism spectrum disorders (ASD), BD, and SCZ. Within the bounds of each risk locus, we annotated differentially expressed genes in the prefrontal cortex of ASD, BD, and SCZ cases vs. controls from PsychENCODE (44). We also annotated genes from exome sequencing studies, including genes with a gene burden p-value < 2.5 x 10 -6 from SCHEMA(45) (SCZ-associated genes), and ASD-associated genes from Satterstrom et al (46) and SFARI Gene (47).…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

“…We studied 21 gene sets with prior evidence for association with neuropsychiatry, as described previously (56,57). Briefly, these gene sets were derived from the following sources: genes identified through GWAS of MDD (7), BD (8), SCZ (58), and neuroticism (59); genes identified through genetic association studies of rare variants, including exome and genome sequencing studies of SCZ (45), autism spectrum disorders (ASD) (46), or other developmental disorders(60), as well as genes intolerant to loss-of-function mutations (61); genes that are differentially expressed in the prefrontal cortex of individuals with BD, SCZ, or ASD (44); genes that have been identified as targets of the RNA binding proteins FMRP, RBFOX2, RBFOX1/3, and CELF4, of the chromatin remodeling genes CHD8, and of the microRNA miR-137 (57,62); genes localized to synapses from SynaptomeDB (63).…”

Section: Effects Of Risk Variants On Quantitative Behavioral and Neur...mentioning

confidence: 99%

Genome-wide significant risk loci for mood disorders in the Old Order Amish founder population

Humphries

Ahn

Kember

et al. 2022

Preprint

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Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n=1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n=314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network analysis suggested that OOA-specific risk loci harbor novel risk-associated genes that interact with known neuropsychiatry-associated genes via gene interaction networks. Annotation of the variants at these risk loci revealed population-enriched, non-synonymous variants in two genes encoding neurodevelopmental transcription factors, CUX1 and CNOT1. Our findings provide insight into the genetic architecture of mood disorders and a substrate for mechanistic and clinical studies.

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“…Bipolar disorder (BD) is a severe disabling psychiatric illness with a genetic basis, and neurodevelopmental origins [Gandal et al, 2018]. Many of the identified genes in BD risk are implicated in neurodevelopmental processes and variations in brain morphology [Mühleisen et al, 2018; Ganesh et al, 2019; Dai et al, 2020; Ithal et al, 2021].…”

Section: Introductionmentioning

confidence: 99%

Abnormalities in migration of neural precursor cells in familial bipolar disorder

Sukumaran

Paul

Guttal³

et al. 2021

Preprint

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Cellular migration is a ubiquitous feature of development that brings brain cells into appropriate spatial relationships. Cortical thinning has been reported in post-mortem brain samples of patients with bipolar disorder (BD). It could be that defective cellular migration during brain development is one of the contributing mechanisms in BD pathogenesis, leading to abnormalities reported at post-mortem, and during brain imaging. To probe the role of cellular migration in BD, we conducted time-lapse analysis of migration of neural precursor cells (NPCs) previously generated in our laboratory. Two NPC lines (B1 and B2) and one control line (C1) were used for the cell migration experiments. Time-lapse images were recorded every 15 min, for 15 hours, and analysed for speed and direction of cellular migration. Abnormalities in cellular migration was a common feature observed in both patient-derived NPCs. Consequently, we investigated underlying mechanistic irregularities in B1 and B2 lines that may contribute to the observed phenotype. To this end, transcriptional changes were compared between the patient-derived cells with the control line. Additionally, we examined exonic variations in genes related to cellular migration or motility. Our analysis showed downregulation of multiple genes that are all part of the EGF/ERBB signaling pathway. Collective dysregulation may be producing the defective cellular phenotype. These cellular migration abnormalities may be linked to structural changes in the brain reported in bipolar disorder.

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Sa75large-Scale Transcriptome-Wide Characterization of Asd, Schizophrenia, and Bipolar Disorder

Cited by 44 publications

References 0 publications

The evolution of knowledge on genes associated with human diseases

The evolution of knowledge on genes associated with human diseases

Genome-wide significant risk loci for mood disorders in the Old Order Amish founder population

Abnormalities in migration of neural precursor cells in familial bipolar disorder

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