The Metabolism of Alcohol: Risk and Protective Factors

Purpose: Abstract for poster submission to VCU Poster Symposium for Undergraduate Research and Creativity Title: The Metabolism of Alcohol: Risk and Protective Factors Background: In 2002, it was reported by the National Institutes of Health that 60.3% of college aged students (18-22) drank alcohol in the past month of being asked, as compared to 51.9% of those not in college. They also found that 20% of college students met the criteria for at least one alcohol use disorder (AUDs)1. Many genes have been linked to an increased risk for AUDs and how individuals with various ethnic backgrounds respond to alcohol. Genes that metabolize alcohol are obvious candidate genes for alcohol-related phenotypes. The purpose of this presentation is to synthesize information about the key genes involved in alcohol metabolism, as documented in the literature. Methods: The information about each gene was found through a literature search using databases including PubMed, Google Scholar, and cited references from relevant papers. For database searches, the names of the genes were used as well as terms such as AUDs, alcohol metabolism, and alcohol and aldehyde dehydrogenase. The focus of the presentation will be relevant to college-aged students, but rely on research done in college and adult populations due to a lack of sufficient college- aged gene-based studies in this area. Results: Alcohol metabolism genes affect how individuals process and respond to alcohol. The main genes that have been studied are alcohol and aldehyde dehydrogenase genes. Alcohol dehydrogenase genes, like ADH1B and ADH1C, first metabolize ethanol (alcohol) into the by-product acetaldehyde and acetaldehyde is then metabolized by aldehyde dehydrogenase genes, like ALDH2, into the waste product acetate2. Many of the adverse effects associated with alcohol consumption are due to the build up of acetaldehyde. Some of these effects include facial blushing, nausea, headaches, and other similar alcohol sensitivity symptoms3,6. Acetaldehyde builds up in an individuals body after alcohol consumption if he or she has a super- active isoenzyme from the ADH1B and/or ADH1C genes and/or a slow ALDH2 enzyme. Individuals with the super-active alcohol dehydrogenase isoenzyme and slow aldehyde dehydrogenase enzyme are less likely to develop AUDs due to the negative effects from excess acetaldehyde in the body4,5,6. However, this also implies that individuals who do not exhibit the described protective phenotype are more likely to endorse increased drinking behaviors and AUDs. Spit for Science: the VCU Student Survey is currently investigating these genes and their association with alcohol consumption and alcohol use disorder symptoms. Due to the diverse nature of the sample, the researchers are able to explore ethnic differences in these alcohol metabolism genes and their effects. Implications: In general, the more public knowledge about these genes and research findings, the more at-risk individuals can get help and diagnosis. A better understanding of aggregate effects of alcohol metabolism genes, as well as more information regarding ethnic differences in the distribution of genetic variants which impact alcohol processing, will assist researchers and health professionals working with those at risk for AUDs.https://scholarscompass.vcu.edu/uresposters/1137/thumbnail.jp

Extending the Apprenticeship of Observation: How Mentee Experience Shape Mentors

Although the importance of mentor teachers in clinical teacher preparation is well established, few researchers explore the social identity development of these individuals. Through our study we contribute to the body of research by exploring mentor teachers\u27 social identity development through the concept of Apprenticeship of Observation - specifically, how they felt their own mentoring experiences influenced their approaches to mentoring. The multi-case study includes findings about mentoring beliefs and practices during the laboratory school component of an Alternate Route to Licensure program. Incorporating semi-structured interviews and video analysis, the findings demonstrate how four mentor teachers\u27 prior experiences as mentees - including Alternate Route to Licensure, traditional teacher preparation programs, and inservice teaching - influenced their interactions with teacher candidates as mentors. Recommendations for practice and implications for future research are provided

Prevalence of Mental Health Disorder Symptoms and Rates of Help-seeking Among University-Enrolled, Black Men

Background. Black men in college represent a subgroup of emerging adults who are at increased risk of developing mental health disorders (MHDs), such as anxiety and depression. Such risk has been attributed to disproportionate experiences with everyday racial discrimination and high levels of psychological distress. Despite being at higher risk, university-enrolled, Black men are not utilizing mental health or health resources at optimal rates. The current evidence base describing prevalence of MHDs and health services utilization among Black men in college is limited. The present study addresses this by examining mental health prevalence among university-enrolled, Black men and their rates of health services utilization. Methods. We analyzed data (N ~ 2500) from a student survey, Spit for Science, a longitudinal, ongoing, research study at a mid-Atlantic, public university. Participants are given surveys in their freshman year and follow-up surveys every spring thereafter. Measures included: mental health disorders (depression and anxiety, as measured by the Symptom Checklist 90) and campus health service utilization (counseling center, health services, wellness center, and recreational sports). We conducted descriptive analyses to determine MHD symptom prevalence and utilization rates; Mann Whitney U tests to compare prevalence rates to White men and Black women; and, Chi-squared tests to compare rates of utilization among groups. Results. During their Freshman year, greater than 60% of students from each ethnic group reported at least one anxiety symptom and greater than 80% reported at least one depressive symptom. By senior year, reporting rates decreased significantly for Black men (49.6%) but remained high for White men (69.1%) and Black women (63%); p \u3c0.000. For depression, results were similar; however, only significant differences between Black men (72.7%) and Black women (87.1%); p\u3c0.000. Black men (20.4%), though reporting high levels of symptoms, still utilized counseling services at lower rates compared to White men (37.76%); p = 0.024. Conclusion. Findings suggest that Black men underutilize available campus health resources despite reporting one or more symptoms associated with anxiety and depression. Further research and prevention efforts are needed to improve help-seeking among this vulnerable population.https://scholarscompass.vcu.edu/gradposters/1077/thumbnail.jp

Patterns of substance use across the first year of college and associated risk factors

Starting college is a major life transition. This study aims to characterize patterns of substance use across a variety of substances across the first year of college and identify associated factors. We used data from the first cohort (N = 2056, 1240 females) of the “Spit for Science” sample, a study of incoming freshmen at a large urban university. Latent transition analysis was applied to alcohol, tobacco, cannabis, and other illicit drug uses measured at the beginning of the fall semester and midway through the spring semester. Covariates across multiple domains – including personality, drinking motivations and expectancy, high school delinquency, peer deviance, stressful events, and symptoms of depression and anxiety – were included to predict the patterns of substance use and transitions between patterns across the first year. At both the fall and spring semesters, we identified three subgroups of participants with patterns of substance use characterized as: (1) use of all four substances; (2) alcohol, tobacco, and cannabis use; and (3) overall low substance use. Patterns of substance use were highly stable across the first year of college: most students maintained their class membership from fall to spring, with just 7% of participants in the initial low substance users transitioning to spring alcohol, tobacco, and cannabis users. Most of the included covariates were predictive of the initial pattern of use, but covariates related to experiences across the first year of college were more predictive of the transition from the low to alcohol, tobacco, and cannabis user groups. Our results suggest that while there is an overall increase in alcohol use across all students, college students largely maintain their patterns of substance use across the first year. Risk factors experienced during the first year may be effective targets for preventing increases in substance use

Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification

Using Patterns of Genetic Association to Elucidate Shared Genetic Etiologies Across Psychiatric Disorders

Twin studies indicate that latent genetic factors overlap across comorbid psychiatric disorders. In this study, we used a novel approach to elucidate shared genetic factors across psychiatric outcomes by clustering single nucleotide polymorphisms based on their genome-wide association patterns. We applied latent profile analysis (LPA) to p-values resulting from genome-wide association studies across three phenotypes: symptom counts of alcohol dependence (AD), antisocial personality disorder (ASP), and major depression (MD), using the European–American case-control genome-wide association study subsample of the collaborative study on the genetics of alcoholism (N = 1399). In the 3-class model, classes were characterized by overall low associations (85.6% of SNPs), relatively stronger association only with MD (6.8%), and stronger associations with AD and ASP but not with MD (7.6%), respectively. These results parallel the genetic factor structure identified in twin studies. The findings suggest that applying LPA to association results across multiple disorders may be a promising approach to identify the specific genetic etiologies underlying shared genetic variance

Attitudes and Opinions About Direct-to-Consumer Genetic Testing in Undergraduate Science Students

Background: There has been exponential growth in the number of direct-to-consumer genetic testing kits sold in the past decade. Consumers utilize direct-to-consumer genetic tests for a number of reasons which include learning about one’s ancestry and potential ways to manage health. Emerging adults tend to be early adopters of new technologies; however, there has been little research regarding the opinions about direct-to-consumer genetic testing in emerging adults. Methods: Data came from a study conducted in an upper-level biology course focusing on understanding undergraduate science students’ overall experiences with receiving personalized genetic testing results from 23andMe. The present study used data collected at the baseline assessment which assessed their opinions and attitudes about direct-to-consumer genetic testing (N=133). Results: Over 80% of participants would recommend direct-to-consumer genetic testing options including carrier status reports, DNA ancestry reports, wellness reports, and trait reports to others. However, participants were not as confident that others would be able to accurately interpret their test results. Additionally, more than two-thirds of the participants stated that they would ask a healthcare provider to help interpret their personalized genetic test results. Conclusions: Participants lack confidence in both their ability to interpret their own results and others to interpret their results. It is important for direct-to-consumer genetic testing companies to educate consumers before providing results in order to minimize potential harms due to misinterpretation of results. Further research is needed to assess motivations to participate in direct-to-consumer genetic testing, impact of testing, and understanding of genetic testing results in emerging adults.https://scholarscompass.vcu.edu/gradposters/1124/thumbnail.jp

Imprinting at the PLAGL1 domain is contained within a 70-kb CTCF/cohesin-mediated non-allelic chromatin loop

Paternal duplications of chromosome 6q24, a region that contains the imprinted PLAGL1 and HYMAI transcripts, are associated with transient neonatal diabetes mellitus. A common feature of imprinted genes is that they tend to cluster together, presumably as a result of sharing common cis-acting regulatory elements. To determine the extent of this imprinted cluster in human and mouse, we have undertaken a systematic analysis of allelic expression and DNA methylation of the genes mapping within an similar to 1.4-Mb region flanking PLAGL1/Plagl1. We confirm that all nine neighbouring genes are biallelically expressed in both species. In human we identify two novel paternally expressed PLAGL1 coding transcripts that originate from unique promoter regions. Chromatin immunoprecipitation for CTCF and the cohesin subunits RAD21 and SMC3 reveals evolutionarily conserved binding sites within unmethylated regions similar to 5 kb downstream of the PLAGL1 differentially methylated region and within the PLAGL1 3' untranslated region (UTR). Higher-order chromatin looping occurs between these regions in both expressing and non-expressing tissues, forming a non-allelic chromatin loop around the PLAGL1/Plagl1 gene. In placenta and brain tissues, we identify an additional interaction between the PLAGL1 P3/P4 promoters and the unmethylated element downstream of the PLAGL1 differentially methylated region that we propose facilitates imprinted expression of these alternative isoforms

Human imprinted retrogenes exhibit non-canonical imprint chromatin signatures and reside in non-imprinted host genes

Imprinted retrotransposed genes share a common genomic organization including a promoter-associated differentially methylated region (DMR) and a position within the intron of a multi-exonic ‘host’ gene. In the mouse, at least one transcript of the host gene is also subject to genomic imprinting. Human retrogene orthologues are imprinted and we reveal that human host genes are not imprinted. This coincides with genomic rearrangements that occurred during primate evolution, which increase the separation between the retrogene DMRs and the host genes. To address the mechanisms governing imprinted retrogene expression, histone modifications were assayed at the DMRs. For the mouse retrogenes, the active mark H3K4me2 was associated with the unmethylated paternal allele, while the methylated maternal allele was enriched in repressive marks including H3K9me3 and H4K20me3. Two human retrogenes showed monoallelic enrichment of active, but not of repressive marks suggesting a partial uncoupling of the relationship between DNA methylation and repressive histone methylation, possibly due to the smaller size and lower CpG density of these DMRs. Finally, we show that the genes immediately flanking the host genes in mouse and human are biallelically expressed in a range of tissues, suggesting that these loci are distinct from large imprinted clusters

Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases)