scholarly journals Parsing Genetically Influenced Risk Pathways: Genetic Loci Impact Problematic Alcohol Use Via Externalizing and Specific Risk

2021 ◽  
Author(s):  
Peter B Barr ◽  
Travis T Mallard ◽  
Sandra Sanchez-Roige ◽  
Holly E Poore ◽  
Richard Karlsson Linner ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Alcohol Misuse ◽  
Genetic Correlations ◽  
Multivariate Methods ◽  
Problematic Alcohol ◽  
Specific Risk ◽  
Polygenic Scores ◽  
Psychiatric Outcomes ◽  
Problematic Alcohol Use

Importance: Characterizing whether genetic variants for psychiatric outcomes operate via specific versus general pathways provides more informative measures of genetic risk, and, potentially, allows us to design more targeted prevention and interventions. Objective: Employ multivariate methods to tease apart variants associated with problematic alcohol use through either general or specific pathways and compare results to standard univariate genetic analysis of problematic alcohol use. Design: We compared results from a univariate genome wide association study (GWAS) of problematic alcohol use to those from a previous multivariate GWAS of externalizing phenotypes. We identified genetic variants associated with problematic alcohol use through a broad liability to externalizing, and those that remain after removing shared variance with externalizing. We compared these results across SNP overlap, bioannotations, genetic correlations, and polygenic scores. Setting: We included GWAS summary statistics from existing GWAS, and two US based hold out samples: The National Longitudinal Study of Adolescent to Adult Health (Add Health) and the Collaborative Study on the Genetics of Alcoholism (COGA). Participants: Publicly available GWAS of externalizing behaviors and participants in Add Health (N=5,107) and COGA (N=7,483), limited to individuals of European ancestries. Exposure(s): N/A Main Outcome(s) and Measure(s): Outcomes included problematic alcohol use (ALCP-O), shared risk for externalizing (EXT), and problematic alcohol use-specific risk (ALCP-S) for the GWASs; a preregistered list of 99 available phenotypes for genetic correlations; and substance use, substance use disorder criteria, and alcohol misuse in the polygenic score analyses. Results: The analysis differentiated SNPs operating through common versus specific risk pathways. While ALCP-O was associated with multiple phenotypes, ALCP-S was predominantly associated with alcohol use and other forms of psychopathology. Polygenic scores for ALCP-O were associated with a variety of other forms of substance use and substance use disorders, polygenic scores for ALCP-S were only associated with alcohol phenotypes. Polygenic scores for both ALCP-S and EXT show differential patterns of associations with alcohol misuse across development. Conclusions and Relevance: Focusing on the differential impacts of shared and specific risk can better characterize pathways of risk for alcohol use disorders. Multivariate methods can be a useful tool for studying many psychiatric conditions. Parsing risk pathways will become increasingly relevant as genetic information is incorporated into clinical practice for psychiatric outcomes.

Online interventions for people hospitalized for deliberate self-harm and problematic alcohol use: Lessons learned from the iiAIM trial

2021 ◽  
Vol 85 (2) ◽  
pp. 123-142 ◽  
Author(s):  
Jacob J. Crouse ◽  
Kirsten C. Morley ◽  
Nicholas Buckley ◽  
Andrew Dawson ◽  
Devanshi Seth ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Research Team ◽  
Alcohol Misuse ◽  
Mental Health Problems ◽  
Age Groups ◽  
Lessons Learned ◽  
Deliberate Self Harm ◽  
Problematic Alcohol ◽  
Self Harm ◽  
Problematic Alcohol Use

Deliberate self-harm and suicide affect all age groups, sexes, and regions, and their prevention is a global health priority. Acute alcohol misuse and chronic alcohol misuse are strong, modifiable risk factors, and Internet interventions aiming to reduce alcohol misuse and comorbid mental health problems (e.g., depression) are a promising and effective treatment modality. The research team aimed to evaluate the feasibility and effectiveness of an Internet-based comorbidity intervention primarily aiming to reduce alcohol consumption, and secondarily to reduce readmission for deliberate self-harm and improve psychological outcomes among people hospitalized for deliberate self-harm who also engage in problematic alcohol use. However, due to several barriers to recruitment, the trial could not be completed and was discontinued. The authors present a “Lessons Learned” discussion and describe the Internet Intervention for Alcohol Improvement (iiAIM) trial, discuss the key barriers experienced by the research team, and recommend potential solutions that may help future trials in this area.

Impaired and Incapacitated Rape Victims: Assault Characteristics and Post-Assault Experiences

2009 ◽  
Vol 24 (4) ◽  
pp. 439-457 ◽  
Author(s):  
Heather Littleton ◽  
Amie Grills-Taquechel ◽  
Danny Axsom
Keyword(s):  
Substance Use ◽  
Sexual Assault ◽  
Alcohol Use ◽  
Future Research ◽  
Rape Victims ◽  
Self Blame ◽  
Problematic Alcohol ◽  
Assault Victims ◽  
Problematic Alcohol Use ◽  
Assault Characteristics

Alcohol is the most common “rape drug,” with up to two-thirds of victims consuming alcohol prior to the assault. Surprisingly, little research has examined the assault and postassault experiences of victims who were impaired or incapacitated as a result of substance use, including alcohol, during a rape. Thus, the current study evaluated the assault and postassault experiences of a sample of 340 nonimpaired, impaired, and incapacitated college rape victims. Results supported that these three groups differed in several assault characteristics, including threats by the assailant, resistance by the victim, and relationship with the assailant. In addition, impairment and incapacitation were associated with several postassault factors, including self-blame, stigma, and problematic alcohol use. Results also highlighted similarities in victims’ experiences, including levels of postassault distress. Implications of the findings for future research investigating impaired and incapacitated sexual assault victims are discussed.

scholarly journals Meta-analysis of problematic alcohol use in 435,563 individuals identifies 29 risk variants and yields insights into biology, pleiotropy and causality

2019 ◽  
Author(s):  
Hang Zhou ◽  
Julia M. Sealock ◽  
Sandra Sanchez-Roige ◽  
Toni-Kim Clarke ◽  
Daniel Levey ◽  
...  
Keyword(s):  
Substance Use ◽  
Alcohol Use ◽  
Genetic Relationships ◽  
Meta Analysis ◽  
European Ancestry ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Problematic Alcohol ◽  
Risk Variants ◽  
Problematic Alcohol Use

AbstractProblematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies (GWASs) have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU combining alcohol use disorder and problematic drinking in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n=67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in genomic conserved and regulatory regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior, and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other outcomes.

scholarly journals Detection of Problematic Substance Use in the Child Welfare System: A Comparison of Self-Report and Caseworker Report

2018 ◽  
Vol 24 (2) ◽  
pp. 152-160 ◽  
Author(s):  
Kristen D. Seay
Keyword(s):  
Substance Use ◽  
Child Welfare ◽  
Alcohol Use ◽  
Drug Use ◽  
Well Being ◽  
National Sample ◽  
Self Report ◽  
Problematic Alcohol ◽  
Problematic Drug ◽  
Problematic Alcohol Use

Using a national sample of American families investigated for child maltreatment, this article compares parental self-report on the Alcohol Use Disorders Identification Test and Drug Abuse Screening Test measures to caseworker report of problematic alcohol and drug use at investigation. Data in this article are from child welfare caseworkers and a subset of parents surveyed in the National Survey of Child and Adolescent Well-Being II—primary caregivers (most often the biological mother) whose child remained in the home following investigation ( n = 4,009). Caseworkers identified problematic alcohol use in only 17.7% of the parents who self-reported problematic alcohol use and problematic drug use in 37.6% of the parents who self-reported problematic drug use. Sensitivity and specificity for the detection of problematic alcohol use were 21.5% and 94.8%, respectively, and 65.3% and 83.7% for problematic drug use, respectively. After controlling for the other variables in the model, an allegation of substance use reduced the odds of caseworker detection of problematic alcohol use being consistent with parent self-report (odds ratio [ OR] = 0.45, p < .01) and the odds of caseworker detection of problematic drug use being consistent with parent self-report ( OR = 0.13, p < .001).

scholarly journals Genome- and Transcriptome-wide Splicing Associations with Problematic Alcohol Use and Alcohol Use Disorder

2021 ◽  
Author(s):  
Spencer B. Huggett ◽  
Ami S. Ikeda ◽  
Qingyue Yuan ◽  
Chelsie E. Benca-Bachman ◽  
Rohan H.C. Palmer
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Association Studies ◽  
Brain Regions ◽  
Mrna Splicing ◽  
Sequencing Data ◽  
Problematic Alcohol ◽  
Alternative Mrna Splicing ◽  
Polygenic Scores ◽  
Problematic Alcohol Use

ABSTRACTGenetic mechanisms of alternative mRNA splicing have been shown in the brain for a variety of neuropsychiatric traits, but not substance use disorders. Our study used RNA-sequencing data on alcohol use disorder (AUD) in the brain’s reward circuitry (n=56; ages 40-73; 100% ‘Caucasian’; four brain regions) and genome-wide association data on problematic alcohol use (n=435,563, ages 22-90; 100% European-American) to investigate potential genetic links with alcohol-related alternative mRNA splicing. Polygenic scores of problematic alcohol use predicted alternative mRNA brain splicing associated with AUD, which depended on brain region. Across brain regions, we found 714 differentially spliced genes in various putative addiction genes and other novel gene targets. We found 6,463 splicing quantitative trait loci (sQTLs) that were associated with the AUD differentially spliced genes. sQTLs were enriched in loose chromatin genomic regions and downstream gene targets. Additionally, the heritability of problematic alcohol use was significantly enriched for DNA variants in and around differentially spliced genes associated with AUD. Our study also performed splicing transcriptome-wide association studies (TWASs) of problematic alcohol use and other drug use traits that unveiled individual genes for follow-up and robust splicing correlations across SUDs. Finally, we show that differentially spliced genes associated showed significant overlap in primate models of chronic alcohol consumption at the gene-level in similar brain regions. Altogether, our study illuminates substantial genetic contributions of alternative mRNA splicing in relation to problematic alcohol use and AUD.

scholarly journals Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use

2021 ◽  
Author(s):  
Spencer B. Huggett ◽  
Emma C. Johnson ◽  
Alexander S. Hatoum ◽  
Dongbing Lai ◽  
Jason A. Bubier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smoking Cessation ◽  
Substance Use ◽  
Alcohol Use ◽  
Gene Set ◽  
Problematic Alcohol ◽  
Gene Sets ◽  
Expression Studies ◽  
Gene Expression Studies ◽  
Problematic Alcohol Use

ABSTRACTBackgroundRodent paradigms and human genome-wide association studies (GWASs) on drug use have the potential to provide biological insight into the pathophysiology of addiction.MethodsUsing GeneWeaver, we created rodent alcohol and nicotine gene-sets derived from 19 gene expression studies on alcohol and nicotine outcomes. We partitioned the SNP-heritability of these gene-sets using four large human GWASs: 1) alcoholic drinks per week, 2) problematic alcohol use, 3) cigarettes per day and 4) smoking cessation. We benchmarked our findings with curated human alcoholism and nicotine addiction gene-sets and performed specificity analyses using other rodent gene-sets (e.g., locomotor behavior) and other human GWASs (e.g., height).ResultsThe rodent alcohol gene-set was enriched for heritability of drinks per week, cigarettes per day, and smoking cessation, but not problematic alcohol use. However, the rodent nicotine gene-set was not significantly associated with any of these traits. Both rodent gene-sets showed enrichment for several non-substance use GWASs, and the extent of this relationship tended to increase as a function of trait heritability. In general, larger gene-sets demonstrated more significant enrichment. Finally, when evaluating human traits with similar heritabilities, both rodent gene-sets showed greater enrichment for substance use traits.ConclusionOur results suggest that rodent gene expression studies can help to identify genes that capture heritability of substance use traits in humans, yet the specificity to human substance use was less than expected due to various factors such as the genetic architecture of a trait. We outline various limitations, interpretations and considerations for future research.

scholarly journals Alcohol use and sexual risk behaviors in the Armed Forces of the Democratic Republic of the Congo

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Bonnie Robin Tran ◽  
Anthony Davis ◽  
Margo Sloan ◽  
Carol Macera ◽  
Anthony Mutombe Mbuyi ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Sexual Behaviors ◽  
Alcohol Misuse ◽  
Armed Forces ◽  
Risky Sexual Behaviors ◽  
Multiple Sexual Partners ◽  
Problematic Alcohol ◽  
Audit Score ◽  
Republic Of The Congo ◽  
Problematic Alcohol Use

Abstract Background Alcohol misuse is an important contributor to sexual acquisition and transmission of HIV in military communities. This cross-sectional study quantified the prevalence of probable problematic alcohol use among male service members in the Armed Forces of the Democratic Republic of the Congo (FARDC), identified associated factors, and investigated associations of alcohol misuse with risky sexual behaviors. Methods Participants included 2549 active duty male soldiers ≥ 18 years old. Data were collected via computer-assisted personal-interview from October 2013–April 2014. The Alcohol Use Disorders Identification Test (AUDIT) was used to identify probable problematic alcohol use (AUDIT score ≥ 8) compared to no/low-risk alcohol use (AUDIT score ≤ 7). Bivariate logistic regressions were used to identify factors associated with probable problematic alcohol use. Several multivariable logistic regressions (adjusted for age, marital status, education level) were used to examine associations of probable problematic alcohol use with risky sexual behaviors. Tests were two sided; statistical significance was defined as p < 0.05. Results Fifteen percent of men screened positive for probable problematic alcohol use. The odds of probable problematic alcohol use were elevated among men who were single and living with a partner (OR = 1.66; 95% CI = 1.24–2.21), ranked as a non-commissioned officer [NCO] (OR = 1.40; 95% CI = 1.10–1.77), and in the 30–39 and 40–49 age groups (OR 30–39 age group = 2.17; 95% CI = 1.56–3.02; OR 40–49 age group = 1.79; 95% CI = 1.26–2.55). Probable problematic alcohol use was associated with increased odds of having sex with a sex worker (SW), having multiple sexual partners, and participating in transactional sex (aOR sex with a SW = 2.36; 95% CI = 1.78–3.13; aOR multiple sexual partners = 2.08; 95% CI = 1.66–2.60; aOR transactional sex = 1.99; 95% CI = 1.59–2.50). Conclusions Results emphasize the need to address alcohol use in the FARDC and integrate alcohol abuse education into HIV prevention programs among male service members. Alcohol abuse prevention efforts should target men who are 30–49 years of age, unmarried, and ranked as a NCO. Messages and interventions to reduce alcohol misuse in relation to risky sexual behaviors are needed.

scholarly journals Differential shared genetic influences on anxiety with problematic alcohol use compared to alcohol consumption.

2020 ◽  
Author(s):  
Sarah Mary Carlton Colbert ◽  
Scott A Funkhouser ◽  
Emma C Johnson ◽  
Charles A Hoeffer ◽  
Marissa A Ehringer ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Genetic Correlations ◽  
Well Being ◽  
Genetic Covariance ◽  
Functional Annotations ◽  
Problematic Alcohol ◽  
Positive Correlations ◽  
Genomic Regions ◽  
Problematic Alcohol Use

Anxiety disorders and alcohol use disorders are common psychiatric illnesses. Comorbidity of the two disorders can have a tremendous effect on treatment of one or both disorders, as well as an individual's social, economic, and physical well-being. We estimated genome-wide genetic correlations between anxiety and alcohol use traits using linkage disequilibrium score regression (LDSC) and found strong and positive correlations of anxiety with problematic alcohol use (PAU), but not with most alcohol consumption (AC) measures. We observed strong, positive between-sex genetic correlations for all traits, but found suggestive evidence that the genetic correlation between alcohol use and anxiety might differ between males and females. Estimates of local genetic covariance demonstrated divergent genetic covariance profiles of PAU and AC with anxiety phenotypes and localized 12 specific genomic regions that likely contribute to both anxiety and alcohol use. Finally, partitioning the genetic covariance among functional annotations also identified the amygdala, caudate basal ganglia and frontal cortex as contributing significantly to positive genetic covariance between anxiety and PAU phenotypes. This study serves as a framework for an approach to be used in future analyses of the genetics of comorbid disorders.

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