Indigenous data protection in wastewater surveillance: balancing public health monitoring with privacy rights DOI Open Access
Melissa L. Perreault, Lawrence Goodridge

Genomic psychiatry :, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 6

Published: Feb. 25, 2025

Wastewater-based epidemiology (WBE) has revolutionized public health surveillance by enabling real-time monitoring of disease patterns across populations through analysis community wastewater. This innovative approach provides precise geographical tracking pathogen levels and spread detecting viral RNA bacterial DNA signatures. Beyond detection, wastewater reveals comprehensive data, including human genomic information biomarkers prescription medication substance use patterns. For Indigenous populations, whose communities often occupy distinct areas, this detailed biological data collection raises significant privacy ethical concerns, particularly given historical research exploitation. By examining international case studies, we analyze instances where traditional knowledge have been misused in psychiatric neuroscience contexts, highlighting violations informed consent principles, sovereignty rights, reinforcement harmful stereotypes. The current regulatory gap ethics necessitates the development specialized WBE protocols for communities. These guidelines must balance benefits with stringent protections authentic engagement governance rights recognition. framework supports both epidemiological advancement protection communities’ autonomy age surveillance.

Language: Английский

Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci DOI Creative Commons
Joseph D. Deak, Hang Zhou, Marco Galimberti

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(10), P. 3970 - 3979

Published: July 25, 2022

Abstract Despite the large toll of opioid use disorder (OUD), genome-wide association studies (GWAS) OUD to date have yielded few susceptibility loci. We performed a large-scale GWAS in individuals European (EUR) and African (AFR) ancestry, optimizing genetic informativeness by performing MTAG (Multi-trait analysis GWAS) with genetically correlated substance disorders (SUDs). Meta-analysis included seven cohorts: Million Veteran Program, Psychiatric Genomics Consortium, iPSYCH, FinnGen, Partners Biobank, BioVU, Yale-Penn 3, resulting total N = 639,063 ( cases 20,686;N effective 77,026) across ancestries. were defined as having lifetime diagnosis, controls anyone not known meet criteria. estimated SNP-heritability (h 2 SNP ) correlations (r g ). Based on correlation, we OUD, alcohol (AUD), cannabis (CanUD). A leave-one-out polygenic risk score (PRS) was compare OUD-MTAG PRS predictors case status 3. The EUR meta-analysis identified three significant (GWS; p ≤ 5 × 10 − 8 lead SNPs—one at FURIN (rs11372849; 9.54 two OPRM1 variants (rs1799971, 4.92 09 ; rs79704991, 1.11 08 r 0.02). Rs1799971 (p 4.91 another variant (rs9478500; 1.95 0.03) cross-ancestry meta-analysis. Estimated h 12.75%, strong CanUD 0.82; 1.14 47 AUD 0.77; 6.36 78 resulted equivalent 128,748 18 independent GWS loci, some mapping genes or gene regions that previously been associated psychiatric addiction phenotypes. accounted for 3.81% variance (beta 0.61;s.e. 0.066; 2.00 16 compared 2.41% 0.45; s.e. 0.058; 2.90 13 explained PRS. current study associations , single OUD-MTAG. architecture is likely influenced both OUD-specific loci shared SUDs.

Language: Английский

Citations

78
Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes DOI
Sylvanus Toikumo,

Mariela Jennings,

Benjamin K. Pham

et al.

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: 8(6), P. 1177 - 1193

Published: April 17, 2024

Language: Английский

Citations

17
Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease DOI Creative Commons
Xianjun Dong, Yunfei Bai, Zhixiang Liao

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 18, 2023

Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identify over 11,039 circRNAs expressed vulnerable dopamine pyramidal neurons laser-captured from 190 brains non-neuronal using ultra-deep, total RNA sequencing. 1526 3308 are custom-tailored to the cell identity of enriched synapse pathways. 29% Parkinson's 12% Alzheimer's disease-associated genes produced validated circRNAs. circDNAJC6, which transcribed a juvenile-onset gene, already dysregulated during prodromal, onset stages common disease neuropathology. Globally, addiction-associated preferentially produce neurons, autism-associated cancers cells. This study shows that tailored neuron implicate circRNA-regulated synaptic specialization diseases.

Language: Английский

Citations

36
Mapping medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq DOI Creative Commons
Bernardo Aguzzoli Heberle, J. Anthony Brandon, Madeline L. Page

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: May 22, 2024

Abstract Determining whether the RNA isoforms from medically relevant genes have distinct functions could facilitate direct targeting of for disease treatment. Here, as a step toward this goal neurological diseases, we sequenced 12 postmortem, aged human frontal cortices (6 Alzheimer cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell per sample. We identified 1,917 expressing multiple in cortex where 1,018 had with different protein-coding sequences. Of these genes, 57 are implicated brain-related diseases including major depression, schizophrenia, Parkinson’s disease. Our study also uncovered 53 new several isoform was most highly expressed that gene. reported on five mitochondrially encoded, spliced isoforms. found 99 differentially between controls.

Language: Английский

Citations

13
Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction DOI Creative Commons
Yousef Tizabi, Bruk Getachew, Sheketha R. Hauser

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 558 - 558

Published: May 30, 2024

Mood disorders and substance use disorder (SUD) are of immense medical social concern. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, it is only relatively recently that the role glia these attracted attention. Detailed understanding glial functions devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contributions neurotrophic factors, neuroinflammation, gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes, synantocytes) phenotypic manifestation or SUD emphasized. addition, knowledge potential development therapeutics touched upon.

Language: Английский

Citations

13
Neuroendocrine mechanisms in the links between early life stress, affect, and youth substance use: A conceptual model for the study of sex and gender differences DOI Creative Commons
Alexandra Donovan, Shervin Assari, Christine E. Grella

et al.

Frontiers in Neuroendocrinology, Journal Year: 2024, Volume and Issue: 73, P. 101121 - 101121

Published: Jan. 20, 2024

Language: Английский

Citations

9
Neurogenetic and multi‐omic sources of overlap among sensation seeking, alcohol consumption, and alcohol use disorder DOI Creative Commons
Alex P. Miller, Ian R. Gizer

Addiction Biology, Journal Year: 2024, Volume and Issue: 29(2)

Published: Jan. 29, 2024

Sensation seeking is bidirectionally associated with levels of alcohol consumption in both adult and adolescent samples, shared neurobiological genetic influences may part explain these associations. Links between sensation use disorder (AUD) primarily manifest via increased rather than through direct effects on increasing problems consequences. Here the overlap among seeking, consumption, AUD was examined using multivariate modelling approaches for genome-wide association study (GWAS) summary statistics conjunction neurobiologically informed analyses at multiple investigation. Meta-analytic genomic structural equation (GenomicSEM) were used to conduct GWAS AUD. Resulting downstream examine brain tissue enrichment heritability evidence (e.g., stratified GenomicSEM, RRHO, correlations neuroimaging phenotypes), identify regions likely contributing observed across traits H-MAGMA LAVA). Across approaches, results supported neurogenetic architecture characterised by overlapping genes expressed midbrain striatal tissues variants cortical surface area. Alcohol evidenced relation decreased frontocortical thickness. Finally, mediation models provided mediating associations This extends previous research examining critical sources multi-omic which underlie phenotypic

Language: Английский

Citations

9
Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits. DOI Creative Commons
Emma C. Johnson, Dongbing Lai, Alex P. Miller

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

ABSTRACT Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. We conducted a genome-wide association study of defined using the Diagnostic and Statistical Manual Mental Disorders (DSM-NicDep) 61,861 individuals (47,884 European ancestry, 10,231 African 3,746 East Asian ancestry) compared results to other nicotine-related phenotypes. replicated well-known at CHRNA5 locus (lead SNP: rs147144681, p =1.27E-11 ancestry; lead SNP = rs2036527, 6.49e-13 cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid problematic alcohol use, lung cancer, material deprivation, several psychiatric disorders, negative respiratory function educational attainment. A polygenic score predicted DSM-5 tobacco disorder 6 11 individual diagnostic criteria, but none Fagerström Test for Nicotine Dependence (FTND) items, independent NESARC-III sample. In genomic structural equation models, loaded more strongly previously identified factor general addiction liability than did “problematic use” (a combination cigarettes per day by FTND). Finally, was genetically correlated GWAS as electronic health records, suggesting combining wide availability EHR data nuanced criterion-level analyses DSM may produce new insights into genetics this disorder.

Language: Английский

Citations

1
The Genetically Informed Neurobiology of Addiction (GINA) model DOI
Ryan Bogdan, Alexander S. Hatoum, Emma C. Johnson

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 24(1), P. 40 - 57

Published: Nov. 29, 2022

Language: Английский

Citations

28
Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder DOI Creative Commons

Julong Wei,

Tova Y. Lambert, Aditi Valada

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 12, 2023

Abstract Dynamic interactions of neurons and glia in the ventral midbrain mediate reward addiction behavior. We studied gene expression 212,713 single nuclei from 95 individuals with history opioid misuse, without drug exposure. Chronic exposure to opioids was not associated change proportions glial neuronal subtypes, however transcriptomes were broadly altered, involving 9.5 − 6.2% expressed genes within microglia, oligodendrocytes, astrocytes. Genes activation immune response including interferon, NFkB signaling, cell motility pathways upregulated, contrasting down-regulated synaptic signaling plasticity non-dopaminergic neurons. Ventral transcriptomic reprogramming context chronic included 325 that previous genome-wide studies had linked risk substance use traits broader population, thereby pointing heritable architectures genomic organization brain’s circuitry.

Language: Английский

Citations

19