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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., (© 2020 Wiley Periodicals, LLC.)

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., (© 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

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.

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.

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.

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., (Copyright © 2012 by the Research Society on Alcoholism.)

Background: Beliefs, attitudes, and preferences about the risk and benefits of genetic testing are important determinants of willingness to undergo testing., Aims: The purpose of this study was to evaluate the perceived importance of genetic testing for alcohol dependence compared with other multifactorial diseases among African Americans., Methods: Surveys were conducted with 258 participants using the Genetic Psycho-Social Implications (GPSI) questionnaire to evaluate several areas of hypothetical genetic testing for alcohol dependence. Respondents were divided into two groups: those who perceived testing for alcohol dependence to be equally important as testing for cancer and those who did not. Using chi-square, the groups' responses were compared for nine GPSI items measuring beliefs about the severity of alcohol dependence, general benefits of genetic testing, and specific benefits of genetic testing for diabetes, hypertension, or a disease affecting a family member., Results: Nearly 86% of respondents believed that genetic testing for alcoholism was equally as important as testing for cancer. Those who reported parity of importance of alcohol dependence and cancer screening were more likely to believe that alcoholism is a deadly disease (p<0.001) and genetic testing influences health (p<0.001)., Conclusion: African Americans reported favorable attitudes and beliefs in possible availability of susceptibility genetic testing for alcohol dependence. The perceived importance of testing for alcohol dependence was associated with beliefs about the severity of alcoholism and certain benefits of genetic testing in general.

Objective: The sequence and progression of alcohol related life events were investigated in a sample of African Americans and compared with findings from a predominantly Caucasian sample., Methods: Alcohol dependent participants were recruited from treatment facilities. Participants completed the Semi-Structured Assessment for the Genetics of Alcoholism to assess the physical, psychological and social manifestations of alcoholism and related disorders., Results: The sequence and mean age of appearance of alcohol-related life events were similar for this sample of African-American men and women. While there were similarities in the progression of alcohol related life problems between the African American and the Caucasian samples, the frequency of symptom endorsement for most problems was significantly higher in the Caucasian sample., Conclusions: Identifying ethnic differences in the clinical course of alcohol dependence may be of importance in developing treatment plans and assist in the development of culturally sensitive intervention and prevention programs.

Alcohol metabolism involves two key enzymes-alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are several types of ADH and ALDH, each of which may exist in several variants (i.e., isoforms) that differ in their ability to break down alcohol and its toxic metabolite acetaldehyde. The isoforms are encoded by different gene variants (i.e., alleles) whose distribution among ethnic groups differs. One variant of ADH is ADH1B, which is encoded by several alleles. An allele called ADH1 B*3 is unique to people of African descent and certain Native American tribes. This allele is associated with more rapid breakdown of alcohol, leading to a transient accumulation of acetaldehyde. African Americans carrying this allele are less likely to have a family history of alcoholism and experience a less rewarding subjective response to alcohol. Moreover, children of mothers with this allele are less vulnerable to alcohol-related birth defects. The enzyme ALDH1 also is encoded by several alleles. Two of these alleles that are found in African Americans-ALDH1 A1 *2 and ALDH1A1 *3--may be associated with a reduced risk of alcoholism.