Identifying Genetic Variants Associated with Opioid Overdose Mortality
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PROVIDER: PRJNA1120515 | ENA |
REPOSITORIES: ENA
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Project description:Identifying Genetic Variants Associated with Opioid Overdose Mortality
| PRJNA1120514 | ENA
Project description:Dynamic interactions of neurons and glia in the ventral midbrain (VM) mediate reward and addiction behavior. We studied gene expression in 212,713 VM single nuclei from 95 human opioid overdose cases and drug-free controls. Chronic exposure to opioids left numerical proportions of VM glial and neuronal subtypes unaltered, while broadly affecting glial transcriptomes, involving 9.5 - 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes, with prominent activation of the immune response including interferon, NFkB signaling, and cell motility pathways, sharply contrasting with down-regulated expression of synaptic signaling and plasticity genes in VM non-dopaminergic neurons. VM transcriptomic reprogramming in the context of opioid exposure and overdose included 325 genes with genetic variation linked to substance use traits in the broader population, thereby pointing to heritable risk architectures in the genomic organization of the brain’s reward circuitry.
2023-08-18 | GSE240457 | GEO
Project description:Single Nucleus Transcriptomes from the Ventral Midbrain of Opioid Overdose Cases and Controls
| PRJNA1003845 | ENA
Project description:'Single nucleus transcriptomes from the ventral midbrain of opioid overdose cases and controls'
| PRJNA954962 | ENA
Project description:'Single nucleus transcriptomes from the ventral midbrain of opioid overdose cases and controls'
| PRJNA954963 | ENA
Project description:Overdose of acetaminophen (APAP) is the major cause of acute liver failure in the Western world with very limited treatment options. Previous studies from our groups and others have shown that timely activation of liver regeneration is a critical determinant of transplant-free survival of APAP-induced acute liver failure (ALF) patients. We used affy microarrays to explore the mechanisms of transcriptional expression in YAP-KO mice after 300mg/kg APAP overdose.
2021-10-04 | GSE183119 | GEO
Project description:ImportanceOpioid-involved overdose mortality has been on the rise for 2 decades in the US, exacerbated by an unregulated drug supply that is unpredictable and has increasingly contained highly potent fentanyl analogs starting a decade ago.ObjectiveTo determine whether there is a geospatial association between law enforcement drug seizures and opioid-involved overdose mortality in San Francisco.Design, setting, and participantsThis cross-sectional study used location- and time-stamped overdose mortality data from the Office of the Chief Medical Examiner and publicly available crime data from the San Francisco Police Department between 2020 and 2023 to assess whether location and time of law enforcement drug seizures were associated with subsequent opioid-involved overdose mortality. Data were analyzed from January 2020 to September 2023.ExposuresTime-stamped locations of law enforcement drug seizures involving a drug distribution charge.Main outcomes and measuresThe primary outcomes were the time and location of (1) overdose mortality involving any opioid and (2) overdose mortality involving fentanyl or any fentanyl analog. The relative risk (RR) and 95% CIs for endemic and epidemic factors were calculated.ResultsThere were 2653 drug seizure crime events that involved any drug distribution charge and 1833 overdose deaths that tested positive for any opioid or synthetic opioid, including heroin and fentanyl analogs. Within the surrounding 100 meters, law enforcement drug seizures were associated with increase risk of fatal opioid-involved overdoses the day following the drug seizure event (RR, 1.74; 95% CI, 1.06-2.83; P = .03) and elevated risk persisted for 7 days (2 days: RR, 1.55; 95% CI, 1.09-2.21; P = .02; 3 days: RR, 1.45; 95% CI, 1.08-1.93; P = .01; 7 days: RR, 1.27; 95% CI, 1.11-1.46; P = .001). Similar statistically significant spatiotemporal patterns were observed in the 250- and 500-meter spatial bandwidths. Within each space-time kernel, the strength of the association, all of which were statistically significant, dissipated the further away in time and distance from the law enforcement drug seizure event.Conclusions and relevanceThe findings of this cross-sectional study suggest that the enforcement of drug distribution laws to increase public safety for residents in San Francisco may be having an unintended negative consequence of increasing opioid overdose mortality. To reduce overdose mortality, it may be better to focus on evidence-based health policies and interventions.
| S-EPMC11923703 | biostudies-literature
Project description:IntroductionOpioid and sedative/hypnotic drug overdoses are major causes of morbidity in the U.S. This study compares 12-month incidence of fatal unintentional drug overdose, suicide, and other mortality among emergency department patients presenting with nonfatal opioid or sedative/hypnotic overdose.MethodsThis is a retrospective cohort study using statewide, longitudinally linked emergency department patient record and mortality data from California. Participants comprised all residents presenting to a licensed emergency department at least once in 2009-2011 with nonfatal unintentional opioid overdose, sedative/hypnotic overdose, or neither (a 5% random sample). Participants were followed for 1 year after index emergency department presentation to assess death from unintentional overdose, suicide, or other causes, ascertained using ICD-10 codes. Absolute death rates per 100,000 person years and standardized mortality ratios relative to the general population were calculated. Data were analyzed February-August 2019.ResultsFollowing the index emergency department visit, unintentional overdose death rates per 100,000 person years were 1,863 following opioid overdose, 342 following sedative/hypnotic overdose, and 31 for reference patients without an index overdose (respective standardized mortality ratios of 106.1, 95% CI=95.2, 116.9; 24.5, 95% CI=21.3, 27.6; and 2.6, 95% CI=2.2, 3.0). Suicide mortality rates per 100,000 were 319, 174, and 32 following opioid overdose, sedative/hypnotic overdose, and reference visits, respectively. Natural causes mortality rates per 100,000 were 8,058 (opioid overdose patients), 17,301 (sedative/hypnotic overdose patients), and 3,097 (reference patients).ConclusionsEmergency department patients with nonfatal opioid or sedative/hypnotic drug overdose have exceptionally high risks of death from unintentional overdose, suicide, and other causes. Emergency department-based interventions offer potential for reducing these patients' overdose and other mortality risks.
| S-EPMC7311279 | biostudies-literature
Project description:Opioids analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It has been recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. Further study indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital acquired bacterial infection. In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital acquired bacterial infection. Citrobacter rodentium is a natural mouse pathogen that models intestinal infection by enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and causes attaching and effacing lesions and colonic hyperplasia. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) increase in virulence factors expression with C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This is the first study to demonstrate that morphine promotes pathogen dissemination in the context of intestinal C. rodentium infection, indicating morphine modulates virulence factor-mediated adhesion of pathogenic bacteria and induces disruption of mucosal host defense during C. rodentium intestinal infection in mice. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and increased risk of infections, suggesting over-prescription of opioids may increase the risk in the emergence of pathogenic strains and should be used cautiously. Therapeutics directed at maintaining gut homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.
2020-02-18 | E-MTAB-7503 | biostudies-arrayexpress
Project description:Opioid abuse poses significant risk to individuals in the United States and epigenetic changes are a leading potential biomarker of opioid abuse. Current evidence, however, is mostly limited to candidate gene analysis in whole blood. Here, we provide Illumina HumanMethylationEPIC array data generated in dorsolateral prefrontal cortex tissue from 153 deceased invidiuals: 72 who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Using these data, we conducted an epigenome-wide association study and identified one CpG site within a gene (NTN1) that may be related to opioid use. We also detected accelerated PhenoAge in opioid samples compared to control samples.
2021-04-01 | GSE164822 | GEO