Associations and Interactions Between SNPs in the Alcohol Metabolizing Genes and Alcoholism Phenotypes in European Americans

Background:  Alcohol dependence is a major cause of morbidity and mortality worldwide and has a strong familial component. Several linkage and association studies have identified chromosomal regions and/or genes that affect alcohol consumption, notably in genes involved in the 2-stage pathway of alcohol metabolism.
Methods:  Here, we use multiple regression models to test for associations and interactions between 2 alcohol-related phenotypes and SNPs in 17 genes involved in alcohol metabolism in a sample of 1,588 European American subjects.
Results:  The strongest evidence for association after correcting for multiple testing was between rs1229984, a nonsynonymous coding SNP in ADH1B, and DSM-IV symptom count ( p  =   0.0003). This SNP was also associated with maximum number of drinks in 24 hours ( p  =   0.0004). Each minor allele at this SNP predicts 45% fewer DSM-IV symptoms and 18% fewer max drinks. Another SNP in a splice site in ALDH1A1 (rs8187974) showed evidence for association with both phenotypes as well ( p  =   0.02 and 0.004, respectively), but neither association was significant after accounting for multiple testing. Minor alleles at this SNP predict greater alcohol consumption. In addition, pairwise interactions were observed between SNPs in several genes ( p  =   0.00002).
Conclusions:  We replicated the large effect of rs1229984 on alcohol behavior, and although not common (MAF = 4%), this polymorphism may be highly relevant from a public health perspective in European Americans. Another SNP, rs8187974, may also affect alcohol behavior but requires replication. Also, interactions between polymorphisms in genes involved in alcohol metabolism are likely determinants of the parameters that ultimately affect alcohol consumption.     

Antisocial behavioral syndromes and DSM-IV alcohol use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions

BACKGROUND: Antisocial personality disorder (ASPD), syndromal adult antisocial behavior (AABS) without conduct disorder (CD) before age 15, and CD without progression to ASPD ("CD only") are highly prevalent among adults with alcohol use disorders (AUDs). Among patients in AUD treatment, antisocial behavioral syndromes are associated with more severe AUDs and poorer treatment outcomes. Comparative data concerning associations of antisocial syndromes with clinical characteristics of AUDs and the sociodemographic and clinical correlates of these syndromes among general population adults with AUDs have not previously been available. This study examines prevalences and correlates of antisocial syndromes among adults with lifetime Diagnostic and Statistical Manual--Version IV (DSM-IV) AUDs, and describes associations of these syndromes with clinical characteristics of AUDs, in the general U.S. population. METHODS: This report is based on the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n=43,093, response rate=81%). Respondents (n=11,843) with lifetime AUDs were classified according to whether they met criteria for ASPD, AABS, "CD only," or no antisocial syndrome. Correlates of antisocial syndromes were examined using contingency table approaches and normal theory analyses of variance. Associations of antisocial syndromes with clinical characteristics of AUDs, including number of lifetime episodes, duration of longest or only episode, and alcohol consumption during period of heaviest drinking were examined using normal theory and logistic regression. RESULTS: Sociodemographic and clinical correlates of antisocial syndromes among respondents with AUDs were consistent with results from prior studies. Antisocial syndromes were significantly associated with phenomenology of AUDs, particularly ASPD with the most severe clinical presentations. Associations with AABS were similar to but more modest than those with ASPD; those with "CD only" were weaker and less consistent. Patterns of associations between antisocial syndromes and clinical characteristics of AUDs were generally similar between men and women. CONCLUSIONS: Antisocial syndromes, particularly ASPD, appear to identify a more pernicious clinical profile of AUDs among adults in the general U.S. population.     

Associations of ALDH2 and ADH1B Genotypes With Alcohol-Related Phenotypes in Asian Young Adults

Background:  Associations of ALDH2 and ADH1B genotypes with alcohol use have been evaluated largely using case–control studies, which typically focus on adult samples and dichotomous diagnostic outcomes. Relatively fewer studies have evaluated ALDH2 and ADH1B in relation to continuous drinking outcomes or at different developmental stages. This study examined additive and interactive effects of ALDH2 and ADH1B genotypes on drinking behavior in a mixed-gender sample of Asian young adults, focusing on continuous phenotypes (e.g., heavy episodic and hazardous drinking, alcohol sensitivity, drinking consequences) whose expression is expected to precede the onset of alcohol use disorders.
Methods:  The sample included 182 Chinese- and Korean-American young adults ages 18 years and older (mean age = 20 years). Effects of ALDH2 , ADH1B and ethnicity were estimated using generalized linear modeling.
Results:  The ALDH2*2 allele predicted lower reported rates of alcohol use and drinking consequences as well as greater reported sensitivity to alcohol. There were significant ethnic group differences in drinking outcomes, such that Korean ethnicity predicted higher drinking rates and lower alcohol sensitivity. ADH1B status was not significantly related to drinking outcomes.
Conclusions:  Ethnicity and ALDH2 status, but not ADH1B status, consistently explained significant variance in alcohol consumption in this relatively young sample. Results extend previous work by showing an association of ALDH2 genotype with drinking consequences. Findings are discussed in the context of possible developmental and population differences in the influence of ALDH2 and ADH1B variations on alcohol-related phenotypes.