Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease DOI Creative Commons
Aaron Z. Wagen, Regina H. Reynolds, Jia Nee Foo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Abstract It is hypothesised that peripheral immune states responding to regional environmental triggers contribute central neurodegeneration. Region-specific genetic selection pressures require this hypothesis be assessed in an ancestry specific manner. Here we utilise genome-wide association studies and expression quantitative trait loci from African, East Asian European ancestries show genes causing neurodegeneration are preferentially expressed innate rather than adaptive cells, of these mediates the risk neurodegenerative disease monocytes ancestry-specific

Language: Английский

How epigenetics impacts stroke risk and outcomes through DNA methylation: A systematic review DOI
Cristina Gallego-Fábrega, Natàlia Cullell, Israel Fernández‐Cadenas

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

The impact of DNA methylation (DNAm) on epigenetics has gained prominence in recent years due to its potential influence ischemic stroke (IS) and treatment outcomes. DNAm is reversible a better understanding role IS could help identify novel therapeutic targets. aim this systematic review was compile the available data risk prognosis explore potential. process followed PRISMA criteria. We searched Pubmed Cochrane databases studies that used hypothesis free methodological approaches. Of 459 identified, 34 met inclusion were categorized as follows: IS; outcomes; age. Most genotyping array technology rather than whole-genome sequencing. testing mainly based blood samples. involved European cohorts. performed at single-center with recruitment time stroke. In few studies, health status determined longitudinally. This shows patients are biologically older expected present characteristic patterns related These be develop new treatments epidrugs.

Language: Английский

Citations

0
Towards equitable brain genomics research, for us by us DOI
Kafui Dzirasa,

Gwenaëlle E. Thomas,

Alvin C Hathaway

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(6), P. 1021 - 1023

Published: May 20, 2024

Language: Английский

Citations

1
RFMix-reader: Accelerated reading and processing for local ancestry studies DOI
Kynon JM Benjamin

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 17, 2024

Local ancestry inference is a powerful technique in genetics, revealing population history and the genetic basis of diseases. It particularly valuable for improving eQTL discovery fine-mapping admixed populations. Despite widespread use RFMix software local inference, large-scale genomic studies face challenges high memory consumption processing times when handling output files.

Language: Английский

Citations

1
Integrated Single-Cell Multiomic Profiling of Caudate Nucleus Suggests Key Mechanisms in Alcohol Use Disorder DOI Creative Commons
Nicholas Green, Hongyu Gao, Xiaona Chu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

Abstract Alcohol use disorder (AUD) induces complex transcriptional and regulatory changes across multiple brain regions including the caudate nucleus, which remains understudied. Using paired single-nucleus RNA-seq ATAC-seq on samples from 143 human postmortem brains, 74 with AUD, we identified 17 distinct cell types. We found that a significant portion of alcohol-induced in gene expression occurred through altered chromatin accessibility. Notably, novel accessibility differences medium spiny neurons, impacting pathways such as RNA metabolism immune response. A small cluster D1/D2 hybrid neurons showed differences, suggesting unique role AUD. Microglia exhibited activation states deviating classical M1/M2 designations, astrocytes entered reactive state partially regulated by JUND , affecting glutamatergic synapse pathways. Oligodendrocyte dysregulation, driven part OLIG2 was linked to demyelination increased TGF-β1 signaling microglia astrocytes. also observed microglia-astrocyte communication via IL-1β pathway. Leveraging our multiomic data, performed type-specific quantitative trait loci analysis, integrating public genome-wide association studies identify AUD risk genes ADAL PPP2R3C providing direct link between genetic variants, accessibility, These findings not only provide new insights into cellular mechanisms related but demonstrate broader utility large-scale uncovering regulation diverse types, has implications beyond substance field.

Language: Английский

Citations

1
The neuroscience of mental illness: Building toward the future DOI
Joshua A. Gordon, Kafui Dzirasa, Frederike H. Petzschner

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(21), P. 5858 - 5870

Published: Oct. 1, 2024

Language: Английский

Citations

1
Integrated Transcriptome Analysis Reveals Novel Molecular Signatures for Schizophrenia Characterization DOI Creative Commons

Tong Ni,

Yu Sun,

Zefeng Li

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 12(2)

Published: Nov. 20, 2024

Abstract Schizophrenia (SCZ) is a complex psychiatric disorder presenting challenges for characterization. The current study aimed to identify and evaluate disease‐responsive essential genes (DREGs) enhance the molecular characterization of SCZ. RNA‐sequencing data from PsychENCODE (536 SCZ patients, 832 controls) peripheral blood transcriptome 144 recruited subjects (59 6 non‐SCZ 79 are analyzed. Shared differential expression obtained using three algorithms. Support vector machine (SVM)‐based recursive feature elimination employed DREGs. biological relevance these DREGs examined through protein–protein interaction network, pathway enrichment, polygenic scoring, brain tissue expression. Key validated in animal models. A DREGs‐based machine‐learning model developed its performance assessed multiple datasets. analysis identified 184 forming an interconnected network involved synaptic plasticity, inflammation, neuronal development, neurotransmission. exhibited distinct SCZ‐related regions Their genetic contributions comparable genome‐wide risk scores. DREG‐based SVM demonstrated high (AUC 85% characterization, 79% specificity). These findings provide new insights into mechanisms underlying emphasize potential improving

Language: Английский

Citations

1
Cell type-specific expression of angiotensin receptors in the human lung with implications for health, aging, and chronic disease DOI Creative Commons
Kynon JM Benjamin, Maor Sauler,

Hataya Poonyagariyagorn

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 22, 2024

The renin-angiotensin system is a highly characterized integrative pathway in mammalian homeostasis whose clinical spectrum has been expanded to lung disorders such as chronic obstructive pulmonary disease (COPD)-emphysema, idiopathic fibrosis (IPF), and COVID pathogenesis. Despite this widespread interest, specific localization of receptor family the limited, partially due imprecision available antibody reagents. In study, we establish expression pattern two predominant angiotensin receptors human lung,

Language: Английский

Citations

0
The role of interferon signaling in neurodegeneration and neuropsychiatric disorders DOI Creative Commons
Daniel W. Sirkis, Alexis P. Oddi, Caroline Jonson

et al.

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 3, 2024

Recent advances in transcriptomics research have uncovered heightened interferon (IFN) responses neurodegenerative diseases including Alzheimer's disease, primary tauopathy, Parkinson's TDP-43 proteinopathy, and related mouse models. Augmented IFN signaling is now relatively well established for microglia these contexts, but emerging work has highlighted a novel role IFN-responsive T cells the brain peripheral blood some types of neurodegeneration. These findings complement body literature implicating dysregulated neuropsychiatric disorders major depression post-traumatic stress disorder. In this review, we will characterize integrate our understanding discuss how sex ancestry modulate response, examine potential mechanistic explanations upregulation antiviral-like pathways seemingly non-viral neurological psychiatric disorders.

Language: Английский

Citations

0
Reported race-associated differences in control and schizophrenia post-mortem brain transcriptomes implicate stress-related and neuroimmune pathways DOI Creative Commons
Shawn Simmons, Keon Arbabi, Daniel Felsky

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Nov. 18, 2024

Background The molecular mechanisms underlying racial disparities in schizophrenia (SCZ) illness courses and outcomes are poorly understood. While these differences thought to arise partly through stressful social gradients, little is known about how reflected the brain, nor they might underlie disparate psychiatric outcomes. Methods To better understand neuro-molecular correlates of SCZ, their overlap, we analyzed post-mortem dorsolateral prefrontal cortex (DLPFC) RNAseq data from two racially diverse cohorts CommonMind Consortium (235 reported Black 546 White, 322 SCZ cases 459 controls) using differential expression gene set variation analyses. Results We observed brain that were consistent across race. A combined mega-analysis identified 1,514 genes with (DE) between race groups after accounting for diagnosis other covariates. Functional enrichment analyses upregulation involved stress immune response, highlighting potential role environmental groups. In a race-by-diagnosis interaction analysis, no individual passed statistical significance. However, 109 sets showed statistically significant differences, implicating metabolic pathways. Conclusion Our results suggest uniquely perturbed identify several candidate pathways associated race-dependent manner. underscore importance cohort ascertainment capture population-level pathogenesis.

Language: Английский

Citations

0
Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease DOI Creative Commons
Aaron Z. Wagen, Regina H. Reynolds, Jia Nee Foo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Abstract It is hypothesised that peripheral immune states responding to regional environmental triggers contribute central neurodegeneration. Region-specific genetic selection pressures require this hypothesis be assessed in an ancestry specific manner. Here we utilise genome-wide association studies and expression quantitative trait loci from African, East Asian European ancestries show genes causing neurodegeneration are preferentially expressed innate rather than adaptive cells, of these mediates the risk neurodegenerative disease monocytes ancestry-specific

Language: Английский

Citations

0