Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations.

African Americans (AA) have lower prevalence of alcohol dependence and higher subjective response to alcohol than European Americans. Genome-wide association studies (GWAS) have identified genes/variants associated with alcohol dependence specifically in AA; however, the sample sizes are still not large enough to detect variants with small effects. Admixture mapping is an alternative way to identify alcohol dependence genes/variants that may be unique to AA. In this study, we performed the first admixture mapping of DSM-IV alcohol dependence diagnosis, DSM-IV alcohol dependence criterion count, and two scores from the self-rating of effects of ethanol (SRE) as measures of response to alcohol: the first five times of using alcohol (SRE-5) and average of SRE across three times (SRE-T). Findings revealed a region on chromosome 4 that was genome-wide significant for SRE-5 (p value = 4.18E-05). Fine mapping did not identify a single causal variant to be associated with SRE-5; instead, conditional analysis concluded that multiple variants collectively explained the admixture mapping signal. PPARGC1A, a gene that has been linked to alcohol consumption in previous studies, is located in this region. Our finding suggests that admixture mapping is a useful tool to identify genes/variants that may have been missed by current GWAS approaches in admixed populations.

Attitudes and experiences regarding genetic research among persons of African descent.

Minorities are underrepresented in genetic research. This study examined the attitudes, experiences, and willingness of persons of African descent related to participation in genetic research. A total of 272 persons of African descent completed a questionnaire about attitudes and experiences associated with genetic research. Descriptive, Chi-square, and logistic regression were used to examine the impact of attitudes and experiences in predicting the odds of willingness to participate in genetic research. A majority of participants (97%) indicated that they have never participated in genetic research; however, a majority also reported that they would be willing to participate in a genetic study specifically for the detection of risk factors for cancer (87%), diabetes (89%), alcohol use disorder (73%), and Alzheimer's disease (88%). Participants who disagreed that "results from genetic research can explain why some diseases are found more often in some ethnic groups than others" were less likely to be willing to participate in studies related to cancer (OR = 0.16), diabetes (OR = .16), alcohol use disorder (OR = 0.27), and Alzheimer's disease (OR = 0.27). Participants reported limited experiences engaging in genetic research; yet, they overwhelmingly acknowledged the importance of genetic research and expressed willingness to participate in multifactorial genetic studies despite concerns about genetic discrimination, stigma, and/or a potentially poor prognosis. Further research on the underlying reasons why persons of African descent choose to participate in genetic research should be explored and addressed to make research more inclusive and ethically sound.

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk.

Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria.

Genome-wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (eg, ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWAS of DSM-IV AD (primary analysis), DSM-IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7418 (1121 families) European American (EA) individuals from the Collaborative Study on the Genetics of Alcoholism (COGA). Trans-ancestral meta-analyses combined these results with data from 3175 (585 families) African-American (AA) individuals from COGA. In the EA GWAS, three loci were genome-wide significant: rs1229984 in ADH1B for AD criterion count (P = 4.16E-11) and Desire to cut drinking (P = 1.21E-11); rs188227250 (chromosome 8, Drinking more than intended, P = 6.72E-09); rs1912461 (chromosome 15, Time spent drinking, P = 1.77E-08). In the trans-ancestral meta-analysis, rs1229984 was associated with multiple phenotypes and two additional loci were genome-wide significant: rs61826952 (chromosome 1, DSM-IV AD, P = 8.42E-11); rs7597960 (chromosome 2, Time spent drinking, P = 1.22E-08). Associations with rs1229984 and rs18822750 were replicated in independent datasets. Polygenic risk scores derived from the EA GWAS of AD predicted AD in two EA datasets (P < .01; 0.61%-1.82% of variance). Identified novel variants (ie, rs1912461, rs61826952) were associated with differential central evoked theta power (loss - gain; P = .0037) and reward-related ventral striatum reactivity (P = .008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability.

Factors associated with willingness to provide biospecimens for genetics research among African American cancer survivors.

This study evaluated factors associated with willingness to provide biospecimens for cancer genetic research among African American cancer survivors. A total of 200 African American adults diagnosed with breast, colon, and/or prostate cancers completed a self-administered survey. Family history information, beliefs about cancer research, cancer genetics and disparities knowledge, willingness to provide a biospecimen, and demographics were obtained. Chi-square, independent samples t tests, and logistic regression analyses were performed. Overall, 79% of this sample was willing to provide a biospecimen for cancer genetics research. Independent associations of willingness to provide a biospecimen existed among demographics (males (p = 0.041)), those who believed in the importance of genetic causes of cancer (p < 0.001), individuals who believe it is important to participate in genetics research (p < 0.001), and those who indicated they would participate in genetics research to help future generations (p = 0.026). Overall, 12.5-56% of participants demonstrated some level of genetics and cancer disparities. This study identified factors that may be incorporated into future research interventions to engage the African American cancer population in cancer genetics biobanking research.

Interactions Between Alcohol Metabolism Genes and Religious Involvement in Association With Maximum Drinks and Alcohol Dependence Symptoms.

OBJECTIVE: Variations in the genes encoding alcohol dehydrogenase (ADH) enzymes are associated with both alcohol consumption and dependence in multiple populations. Additionally, some environmental factors have been recognized as modifiers of these relationships. This study examined the modifying effect of religious involvement on relationships between ADH gene variants and alcohol consumption-related phenotypes. METHOD: Subjects were African American, European American, and Hispanic American adults with lifetime exposure to alcohol (N = 7,716; 53% female) from the Collaborative Study on the Genetics of Alcoholism. Genetic markers included ADH1Brs1229984, ADH1B-rs2066702, ADH1C-rs698, ADH4-rs1042364, and ADH4-rs1800759. Phenotypes were maximum drinks consumed in a 24-hour period and total number of alcohol dependence symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Religious involvement was defined by self-reported religious services attendance. RESULTS: Both religious involvement and ADH1B-rs1229984 were negatively associated with the number of maximum drinks consumed and the number of lifetime alcohol dependence symptoms endorsed. The interactions of religious involvement with ADH1B-rs2066702, ADH1C-rs698, and ADH4-rs1042364 were significantly associated with maximum drinks and alcohol dependence symptoms. Risk variants had weaker associations with maximum drinks and alcohol dependence symptoms as a function of increasing religious involvement. CONCLUSIONS: This study provided initial evidence of a modifying effect for religious involvement on relationships between ADH variants and maximum drinks and alcohol dependence symptoms.

FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students.

Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T-allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking. © 2016 Wiley Periodicals, Inc.

Beliefs and Preferences for Medical Research Among African-Americans.

BACKGROUND AND OBJECTIVES: Numerous factors contribute to underrepresentation of African-Americans in medical research, including beliefs, historical events, structural, and health access obstacles. This study examined beliefs about medical research and the types of study methods preferred among potential African-American research participants. METHODS: A sample of 304 African-American participants from the Washington, DC Metropolitan area, completed a survey evaluating beliefs about medical research and preferred research study methods. Multiple Regression analyses were performed to examine how age, gender, and education may influence these beliefs and preferences for research study methods. RESULTS: The beliefs and preferences surveyed did not differ by age, gender, or educational attainment. There was an overwhelmingly favorable belief (90 %) that medical research was necessary and assists in finding a cure for a disease. Most respondents preferred participating in research related to issues with which they were familiar (e.g., diabetes, hypertension) or working with researchers of a similar ethnic background to themselves. Interestingly, though nonsignificant, those with higher levels of educational trended toward the belief that participation in research was risky. CONCLUSION: The findings of this study indicate that certain beliefs about medical research participation and preferred study methodologies reported by African-Americans did not differ by age, gender, or level of education. This information about African-American's beliefs and preferences regarding medical research should lead to an awareness of potential gains in African-American participation through the development of culturally sensitive medical research studies and methodologies.

Episode-specific drinking-to-cope motivation and next-day stress-reactivity.

BACKGROUND: Research consistently shows drinking-to-cope (DTC) motivation is uniquely associated with drinking-related problems. We furthered this line of research by examining whether DTC motivation is predictive of processes indicative of poor emotion regulation. Specifically, we tested whether nighttime levels of episode-specific DTC motivation, controlling for drinking level, were associated with intensified affective reactions to stress the following day (i.e. stress-reactivity). DESIGN AND METHODS: We used a micro-longitudinal design to test this hypothesis in two college student samples from demographically distinct institutions: a large, rural state university (N = 1421; 54% female) and an urban historically Black college/university (N = 452; 59% female). RESULTS: In both samples the within-person association between daily stress and negative affect on days following drinking episodes was stronger in the positive direction when previous night's drinking was characterized by relatively higher levels of DTC motivation. We also found evidence among students at the state university that average levels of DTC motivation moderated the daily stress-negative affect association. CONCLUSIONS: Findings are consistent with the notion that DTC motivation confers a unique vulnerability that affects processes associated with emotion regulation.

Perceived racial discrimination and negative-mood-related drinking among African American college students.

OBJECTIVE: Research consistently shows a positive association between racial discrimination and problematic alcohol use among African Americans, but little is known about the micro-processes linking this pernicious form of stress to drinking. One possibility is that the cumulative effects of discrimination increase individuals' likelihood of negative-mood-related drinking. In the current study, we examined whether individual differences in lifetime perceived racial discrimination among African American college students moderate relations between daily negative moods and evening alcohol consumption in both social and nonsocial contexts. METHOD: Data came from an online daily diary study of 441 African Americans (58% female) enrolled at a historically black college/university. Lifetime discrimination was measured at baseline. For 30 days, students reported the number of drinks they consumed the night before both socially and nonsocially, as well as their daytime level of negative mood. RESULTS: In support of the hypotheses, only men who reported higher (vs. lower) lifetime discrimination showed a positive association between daily negative mood and that evening's level of nonsocial drinking. Contrary to expectation, women who reported higher (vs. lower) discrimination showed a negative association between daily negative mood and nonsocial drinking. Neither daily negative mood nor lifetime discrimination predicted level of social drinking. CONCLUSIONS: These findings provide further evidence that the cumulative impact of racial discrimination may produce a vulnerability to negative-mood-related drinking--but only for African American men. Importantly, these effects emerged only for nonsocial drinking, which may further explain the robust association between discrimination and problematic alcohol use.

Drinking to cope among African American college students: an assessment of episode-specific motives.

Despite evidence that African Americans are disproportionately affected by drinking to cope relative to European Americans, African American college students' drinking motives remain understudied. Additionally, most research has only examined between-person differences in drinking to cope as a predictor of alcohol use, ignoring within-person variability. In the current daily diary study of 462 African American undergraduates from a historically Black university, associations between episode-specific drinking to cope motives and alcohol use were tested, an approach more consistent with motivational theories of drinking. At baseline, students completed traditional global drinking motive measures; then for 30 days they reported the number of standard drinks they consumed the previous night, and, if they drank, their coping, enhancement, and social reasons for doing so. Students who reported higher mean levels of episode-specific coping motives, on average, consumed more alcohol on drinking evenings. Furthermore, mean episode-specific coping motives, but not global coping motives, predicted average levels of alcohol use. Additionally, coping motives were particularly important for predicting nonsocial (vs. social) drinking. Finally, during evenings for which students reported higher than usual episode-specific coping motives, men consumed more alcohol in both social and nonsocial contexts; in contrast, women reporting higher than usual drinking-to-cope motives only consumed more nonsocial drinks. In conclusion, drinking among African American college students was related to coping motives, particularly among men and in the context of nonsocial alcohol consumption. Moreover, motivational theories of alcohol use may be refined by measuring episode-specific drinking motives that more accurately capture the drinking-to-cope process.

Genetic testing for the susceptibility to alcohol dependence: interest and concerns in an African American population.

BACKGROUND: The search to identify genes for the susceptibility to alcohol dependence (AD) is generating interest for genetic risk assessment. The purpose of this study is to examine the level of interest and concerns for genetic testing for susceptibility to AD. METHODS: Three hundred four African American adults were recruited through public advertisement. All participants were administered the Genetic Psycho-Social Implication (GPSI) questionnaire, which surveyed their interests in hypothetical genetic testing for AD, as well as their perception of ethical and legal concerns. RESULTS: Over 85% of participants were interested in susceptibility genetic testing; however, persons with higher education (p=0.002) and income (p=0.008) were less willing to receive testing. Perception of AD as a deadly disease (48.60%) and wanting to know for their children (47.90%) were the strongest reasons for interest in testing. Among those not interested in testing, the belief that they were currently acting to lower their risk was the most prevalent. The most widely expressed concern in the entire sample was the accuracy of testing (35.50%). Other notable concerns, such as issues with the method of testing, side effects of venipuncture, falsely reassuring results, and lack of guidelines on "what to do next" following test results, were significantly associated with willingness to receive testing. CONCLUSION: Although an overwhelming majority of participants expressed an interest in genetic testing for AD, there is an understandable high level of methodological and ethical concerns. Such information should form the basis of policies to guide future genetic testing of AD.

Framing ethnic variations in alcohol outcomes from biological pathways to neighborhood context.

BACKGROUND: Health disparities research seeks to eliminate disproportionate negative health outcomes experienced in some racial/ethnic minority groups. This brief review presents findings on factors associated with drinking and alcohol-related problems in racial/ethnic groups. METHODS: Those discussed are as follows: (i) biological pathways to alcohol problems, (ii) gene × stress interactions, (iii) neighborhood disadvantage, stress, and access to alcohol, and (iv) drinking cultures and contexts. RESULTS: These factors and their interrelationships are complex, requiring a multilevel perspective. CONCLUSIONS: The use of interdisciplinary teams and an epigenetic focus are suggested to move the research forward. The application of multilevel research to policy, prevention, and intervention programs may help prioritize combinations of the most promising intervention targets.

Evaluation of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in African Americans.

INTRODUCTION: The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers. MATERIALS: The sample included eighty-seven 21- to 35-year-old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates. RESULTS: Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p < 0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p < 0.001). These observations were mediated by drinks per drinking day, gender, and FHA. CONCLUSIONS: ADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day.

Alcohol dependence and health care utilization in African Americans.

OBJECTIVE: Ethnic and cultural differences in patterns of alcohol use disorders must be understood in order to address improvement in prevention of such disorders and accessibility to health care services. The purpose of this study was to evaluate factors that influence the utilization of medical and mental health services among alcohol-dependent and non-alcohol-dependent African Americans. METHOD: A cohort of 454 African Americans was evaluated. Alcohol-dependent participants were recruited from various inpatient treatment facilities in the Washington, DC, metropolitan area and through advertisement and word of mouth. Non-alcohol-dependent participants were recruited by advertisements. Each participant was administered the Semi-Structured Assessment for the Genetics of Alcoholism to assess alcohol dependency and the Family History Assessment module to access family history of alcoholism. Xl Test and analysis of variance were used to analyze the data. RESULTS: Alcohol dependence was more prevalent among men, those with lower income, those with less education, and they utilized mental health counseling as opposed to medical-based therapy. Increased reports of medical conditions such as migraine (p<.001), loss of consciousness (p=.001), and sexually transmitted diseases: (p<.001) were also associated with alcohol dependency. Other factors, including visits to inpatient treatment programs, were directly related to incidence of alcohol dependency regardless of gender status (p<.001). CONCLUSIONS: This study suggests an association exists among alcohol dependence, medical conditions, health care, and mental care utilization among African Americans. Future research may benefit from investigating if an association exists between alcohol use disorders and health care utilization for other ethnic groups.

Institutional incorporation of screening, brief intervention, and referral to treatment (SBIRT) in residency training: achieving a sustainable curriculum.

The success of implementing a screening, brief intervention and referral to treatment (SBIRT) program within a medical residency program for sustainability is contingent upon a well-crafted training curriculum that incorporates substance abuse education and clinical practice skills. The goal of the Howard University (HU) SBIRT program is to train residents in providing culturally competent evidence-based screening, brief intervention and referral to treatment for patients who have a substance use disorder or who are at risk for developing the disorder. Utilizing the Office of Graduate Medical Education (GME) allows all residents to be trained in SBIRT techniques and receive continuing education in SBIRT and SBIRT-related topics through new resident orientation and the core lecture series. The utilization of Graduate Medical Education office has allowed a robust SBIRT training program to be implemented into medical residency education, contributing to the sustainability of SBIRT as a component of patient care.

Screening, brief intervention, and referral to treatment: public health training for primary care.

OBJECTIVES: The purpose of this study was to elucidate changes in attitudes, experiences, readiness, and confidence levels of medical residents to perform screening, brief intervention, and referral to treatment (SBIRT) and factors that moderate these changes. METHODS: A cohort of 121 medical residents received an educational intervention. Self-reported experience, readiness, attitude, and confidence toward SBIRT-related skills were measured at baseline and at follow-up. Analyses were conducted to evaluate the effects of medical specialization. RESULTS: The intervention significantly increased experience (P<.001), attitude (P<.05), readiness (P<.001), and confidence (P<.001). Residents were more likely to report that their involvement influenced patients' substance use. However, experience applying SBIRT skills varied by country of birth, specialty, and baseline scores. CONCLUSIONS: This study suggested that SBIRT training was an effective educational tool that increased residents' sense of responsibility. However, application of skills might differ by specialization and other variables. Future studies are needed to explore and evaluate SBIRT knowledge obtained, within the context of cultural awareness and clinical skills.

Magnitude of the problem of drinking alcohol on college campuses, commentary on "Structuring a college alcohol prevention program on the low level of response to alcohol model: a pilot model".

BACKGROUND: The objective of this commentary is to discuss the significance of the study entitled, "Structuring a College Alcohol Prevention Program on the Low Level of Response to Alcohol Model: A Pilot Model" by Schuckit and colleagues (2012) published in this issue of the Alcoholism: Clinical and Experimental Research. The work by Schuckit and colleagues emphasizes the importance of personalizing an alcohol prevention program for college students. METHODS: This pilot model is the result of over 30 years of clinical translational research on an individual's level of response to alcohol. The prevention program is efficient, simple, safe, cost-effective and self-directed. RESULTS: The results indicate the computerized intervention was associated with decreases in drinking overall and students with a low level of response to alcohol showed greater decreases when the prevention program is personalized to focus on how level of response is affected by peer influence, alcohol expectancies, and stress management. It concludes that college students with a low level of response to alcohol will benefit from a prevention program that is personalized to this well documented endophenotype. CONCLUSIONS: The findings provide the foundation for developing future longitudinal studies of the proposed prevention program with a larger sample size on diverse campuses. In addition, as mentioned in the Discussion section, future studies could also evaluate the effectiveness of other easily measured clinical endophenotypes known to be associated with alcohol use such as impulsivity, negative effect, and maximum number of drinks per occasion.