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

GenomeMUSter mouse genetic variation service enables multitrait, multipopulation data integration and analysis DOI Creative Commons
Robyn L. Ball, Molly A. Bogue, Hongping Liang

et al.

Genome Research, Journal Year: 2024, Volume and Issue: 34(1), P. 145 - 159

Published: Jan. 1, 2024

Hundreds of inbred mouse strains and intercross populations have been used to characterize the function genetic variants that contribute disease. Thousands disease-relevant traits characterized in mice made publicly available. New including consomics, collaborative cross, expanded BXD, wild-derived add existing complex disease models, mapping populations, sensitized backgrounds for engineered mutations. The genome sequences strains, along with dense genotypes from others, enable integrated analysis trait–variant associations across but these analyses are hampered by sparsity Moreover, data not readily interoperable other resources. To address limitations, we created a uniformly variant resource harmonizing multiple sets. Missing were imputed using Viterbi algorithm data-driven technique incorporates local phylogenetic information, an approach is extendable model organisms. result web- programmatically accessible service called GenomeMUSter, comprising single-nucleotide covering 657 at 106.8 million segregating sites. Interoperation phenotype databases, analytic tools, resources wealth applications, multitrait, multipopulation meta-analysis. We show this cross-species comparisons type 2 diabetes substance use disorder meta-analyses, leveraging likely role human effects Other applications include refinement mapped loci prioritization strain modeling further unlock extant diversity genomic studies health

Language: Английский

Citations

7
Pleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders DOI
Dóra Koller, Eleni Friligkou,

Brendan Stiltner

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(7), P. 2021 - 2030

Published: Feb. 15, 2024

Language: Английский

Citations

6
Why do we focus on the exception and not the rule? Examining the prevalence of mono‐ versus polysubstance use in the general population DOI
Allen J. Bailey, R. Kathryn McHugh

Addiction, Journal Year: 2023, Volume and Issue: 118(10), P. 2026 - 2029

Published: July 12, 2023

Substance use disorders (SUDs) are predominantly studied as drug class specific constructs (e.g. opioid versus alcohol disorder). Polysubstance (PSU), or the of two more substances from multiple classes, is only captured diagnostically by co-occurrences class-specific SUDs, and in many ways relegated to a secondary position within literature. However, this not consistent with mounting empirical evidence regarding high prevalence PSU patterns compared mono-use pattern (i.e. all contained single-drug class). The current study measured how individuals general United States population could be characterized having pattern.We those who used past year, at least symptoms an SUD received treatment for alcohol/drug problems year using data National Survey on Drug Use Health (NSDUH) years 2015-19.Of substance(s) 64% reported pattern. Importantly, 26% had 22% substance pattern.Although drugs common public health level, it much less presentation than polysubstance (PSU) among even mild disorder severity. This means that efforts isolation do focus upon most phenomenon. We discuss importance implications embracing framework misuse disorders.

Language: Английский

Citations

15
Genetic contribution to the comorbidity between attention-deficit/hyperactivity disorder and substance use disorders DOI Creative Commons
Dóra Koller, Marina Mitjans,

Manuela R. Kouakou

et al.

Psychiatry Research, Journal Year: 2024, Volume and Issue: 333, P. 115758 - 115758

Published: Feb. 3, 2024

We characterized the genetic architecture of attention-deficit hyperactivity disorder-substance use disorder (ADHD-SUD) relationship by investigating correlation, causality, pleiotropy, and common polygenic risk. Summary statistics from genome-wide association studies (GWAS) were used to investigate ADHD (Neff=51,568), cannabis (CanUD, Neff=161,053), opioid (OUD, Neff=57,120), problematic alcohol (PAU, Neff=502,272), tobacco (PTU, Neff=97,836). ADHD, CanUD, OUD GWAS meta-analyses included cohorts with case definitions based on different diagnostic criteria. PAU combined information related disorder, dependence, items consequences assessed disorders identification test. PTU was generated a multi-trait analysis including regarding Fagerström Test for Nicotine Dependence cigarettes per day. Linkage disequilibrium score regression analyses indicated positive correlation OUD, PAU, PTU. Genomic structural equation modeling showed that these correlations two latent factors: one other PAU. had larger causal effect than reverse in two-sample Mendelian randomization analyses. Conversely, similar sizes found between CanUD. CADM2 rs62250713 pleiotropic SNP all SUDs. seven, one, twenty-eight variants PTU, respectively. Finally, PRS associated increased odds ADHD. Our findings demonstrated contribution multiple mechanisms comorbidity

Language: Английский

Citations

5
Combining Transdiagnostic and Disorder-Level GWAS Enhances Precision of Psychiatric Genetic Risk Profiles in a Multi-Ancestry Sample DOI Creative Commons
Yousef Khan, Christal N. Davis, Zeal Jinwala

et al.

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

Published: May 10, 2024

Abstract The etiology of substance use disorders (SUDs) and psychiatric reflects a combination both transdiagnostic (i.e., common) disorder-level independent) genetic risk factors. We applied genomic structural equation modeling to examine these factors across SUDs, psychotic, mood, anxiety using genome-wide association studies (GWAS) European-(EUR) African-ancestry (AFR) individuals. In EUR individuals, represented SUDs (143 lead single nucleotide polymorphisms [SNPs]), psychotic (162 SNPs), mood/anxiety (112 SNPs). identified two novel SNPs for that have probable regulatory roles on FOXP1 , NECTIN3 BTLA genes. AFR (1 SNP) (no significant SUD factor SNP, although previously in EUR- cross-ancestry GWAS, is finding Shared variance accounted overlap between their comorbidities, with second-order GWAS identifying up 12 not significantly associated either first-order Finally, common independent effects showed different associations psychiatric, sociodemographic, medical phenotypes. For example, the components schizophrenia bipolar disorder had distinct affective risk-taking behaviors, phenome-wide conditions tobacco broader factor. Thus, combining approaches can improve our understanding co-occurring increase specificity discovery, which critical demonstrate considerable symptom etiological overlap.

Language: Английский

Citations

5
A multivariate approach to understanding the genetic overlap between externalizing phenotypes and substance use disorders DOI Creative Commons
Holly E. Poore, Alexander S. Hatoum, Travis T. Mallard

et al.

Addiction Biology, Journal Year: 2023, Volume and Issue: 28(9)

Published: Aug. 23, 2023

Abstract Substance use disorders (SUDs) are phenotypically and genetically correlated with each other psychological traits characterized by behavioural under‐control, termed externalizing phenotypes. In this study, we used genomic structural equation modelling to explore the shared genetic architecture among six phenotypes four SUDs in two previous multivariate genome‐wide association studies of an addiction risk factor, respectively. We first evaluated five confirmatory factor analytic models, including a common model, alternative parameterizations two‐factor structures bifactor model. next explored correlations between factors identified these models relevant traits. Finally, quantified degree polygenic overlap using MiXeR. found that provided best fit data, evidenced high loadings, good reliability no evidence concerning model characteristics. The yielded ( r g s ≥ 0.87), effect sizes external 0.95). Nevertheless, 21 84 criteria showed small, significant differences factors. MiXer results approximately 81% influential variants were risk, whereas 56% its externalizing. These suggest largely shared, though both constructs also retain meaningful unshared variance. can inform future efforts identify specific influences on SUDs.

Language: Английский

Citations

12
Shared genetic liability for alcohol consumption, alcohol problems, and suicide attempt: Evaluating the role of impulsivity DOI Creative Commons
Mallory Stephenson, Séverine Lannoy, Alexis C. Edwards

et al.

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 10, 2023

Abstract Heavy drinking and diagnosis with alcohol use disorder (AUD) are consistently associated risk for suicide attempt (SA). Though the shared genetic architecture among consumption problems (ACP) SA remains largely uncharacterized, impulsivity has been proposed as a heritable, intermediate phenotype both suicidal behavior. The present study investigated extent to which liability ACP is genetically related five dimensions of impulsivity. Analyses incorporated summary statistics from genome-wide association studies ( N = 160,824), dependence 46,568), alcoholic drinks per week 537,349), 513,497), 22,861), extraversion 63,030). We used genomic structural equation modeling (Genomic SEM) to, first, estimate common factor model consumption, problems, dependence, week, included indicators. Next, we evaluated correlations between this factors representing negative urgency, positive lack premeditation, sensation-seeking, perseverance. Common was significantly correlated all impulsive personality traits examined rs 0.24–0.53, p s < 0.002), largest correlation though supplementary analyses suggested that these findings were potentially more strongly influenced by than SA. These have potential implications screening prevention: Impulsivity can be comprehensively assessed in childhood, whereas heavy quite rare prior adolescence. Our provide preliminary evidence features may serve early indicators suicidality.

Language: Английский

Citations

11
Identifying genetic loci and phenomic associations of substance use traits: A multi‐trait analysis of GWAS (MTAG) study DOI
Heng Xu, Sylvanus Toikumo, Richard C. Crist

et al.

Addiction, Journal Year: 2023, Volume and Issue: 118(10), P. 1942 - 1952

Published: May 9, 2023

Abstract Background and Aims Genome‐wide association studies (GWAS) of opioid use disorder (OUD) cannabis (CUD) have lagged behind those alcohol (AUD) smoking, where many more loci been identified. We sought to identify novel for substance traits (SUTs) in both African‐ (AFR) European‐ (EUR) ancestry individuals enhance our understanding the traits’ genetic architecture. Design used multi‐trait analysis GWAS (MTAG) analyze four SUTs EUR subjects (OUD, CUD, AUD smoking initiation [SMKinitiation]), three AFR trajectory [SMKtrajectory]). conducted gene‐set protein–protein interaction analyses calculated polygenic risk scores (PRS) two independent samples. Setting This study was United States. Participants A total 5692 4918 Yale‐Penn sample 29 054 10 265 Penn Medicine BioBank sample. Findings MTAG identified genome‐wide significant (GWS) single nucleotide polymorphisms (SNPs) all EUR: 41 SNPs 36 OUD; 74 60 CUD; 63 52 AUD; 183 144 SMKinitiation. also GWS AFR: 2 3 1 SNP locus SMKtrajectory. In sample, MTAG‐derived PRS consistently yielded associations with corresponding diagnosis multiple related phenotypes than GWAS‐derived PRS. Conclusions Multi‐trait boosted number found traits, identifying genes not previously linked any substance, increased power scores. can be use, especially which samples are smaller historically legal substances.

Language: Английский

Citations

11
Using deep long-read RNAseq in Alzheimer’s disease brain to assess medical relevance of RNA isoform diversity DOI Creative Commons
Bernardo Aguzzoli Heberle, J. Anthony Brandon, Madeline L. Page

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 7, 2023

Due to alternative splicing, human protein-coding genes average over eight RNA isoforms, resulting in nearly four distinct protein coding sequences per gene. Long-read RNAseq (IsoSeq) enables more accurate quantification of shedding light on their specific roles. To assess the medical relevance measuring isoform expression, we sequenced 12 aged frontal cortices (6 Alzheimer's disease cases and 6 controls; 50% female) using one Oxford Nanopore PromethION flow cell sample. Our study uncovered 53 new high-confidence isoforms medically relevant genes, including several where was most highly expressed for that Specific examples include

Language: Английский

Citations

11
Identification of risk variants and cross-disorder pleiotropy through multi-ancestry genome-wide analysis of alcohol use disorder DOI
Romain Icick, Alexey Shadrin, Børge Holen

et al.

Nature Mental Health, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

Citations

0