We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009.
In conclusion, the present study suggested that the ADH1B Arg47His polymorphism does not contribute to the risk of colorectal adenoma in any subgroup of middle-aged Japanese men defined by alcohol drinking, as well as the ALDH2 Glu487Lys and MTHFR C677T genotypes.
Among conventional markers of alcohol abuse, the mean corpuscular volume (MCV) of erythrocytes is prognostic of alcohol-related cancer and its predictivity increases when combined with functional polymorphisms of alcohol dehydrogenase (ADH1B [rs1229984] and ADH1C [rs698]) and the mitochondrial aldehyde dehydrogenase (ALDH2 [rs671]).
Given the logistic and ethical constraints that would be associated with a trial of alcohol use to prevent depression, we aimed to complete a Mendelian randomization study to determine if a genetic polymorphism associated with alcohol abuse and dependence (ADH1B rs1229984 G-->A) contributed to modulate the risk of depression in a community-derived cohort of older men.
We genotyped the rs1229984 G→A variant of the alcohol dehydrogenase 1B (ADH1B) gene, which is associated with lower prevalence of alcohol abuse and dependence.
Among conventional markers of alcohol abuse, the mean corpuscular volume (MCV) of erythrocytes is prognostic of alcohol-related cancer and its predictivity increases when combined with functional polymorphisms of alcohol dehydrogenase (ADH1B [rs1229984] and ADH1C [rs698]) and the mitochondrial aldehyde dehydrogenase (ALDH2 [rs671]).
We also observed a genome-wide significant association in non-Hispanic whites between the previously reported SNP rs1229984 in ADH1B and both alcohol consumption phenotypes (OR=0.79, P=2.47 × 10<sup>-20</sup> for drinker status and beta=-0.19, P=1.91 × 10<sup>-35</sup> for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, P=4.35 × 10<sup>-7</sup> and beta=-0.21, P=2.58 × 10<sup>-6</sup>, respectively).
Lack of the ADH1B rs1229984 protective allele was significantly associated with consumption- and AUD-related phenotypes (OR = 1.77 for AUD; OR = 1.83 for risk drinking), while lack of the ADH1C rs698 protective allele was significantly associated with AUD-related phenotypes (OR = 2.32 for AUD).
Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity.
This is the first study to show that ADH1B rs1229984 is related to 6 of the 11 DSM-IV AUD criteria and that alcohol consumption explained a significant proportion of these associations and the association of ADH1B with AUDs.
The functional variant rs1229984 in alcohol dehydrogenase 1B (ADH1B) has been associated at a genome-wide level with alcohol use disorders in diverse adult populations.
With longitudinal EHR data from the Million Veteran Program (MVP) linked to genetic data, we used two population-specific polymorphisms in ADH1B that are associated strongly with AUD in African Americans (AAs) and European Americans (EAs): rs2066702 (Arg369Cys, AAs) and rs1229984 (Arg48His, EAs) as criterion measures.
With longitudinal EHR data from the Million Veteran Program (MVP) linked to genetic data, we used two population-specific polymorphisms in ADH1B that are associated strongly with AUD in African Americans (AAs) and European Americans (EAs): rs2066702 (Arg369Cys, AAs) and rs1229984 (Arg48His, EAs) as criterion measures.
Lack of the ADH1B rs1229984 protective allele was significantly associated with consumption- and AUD-related phenotypes (OR = 1.77 for AUD; OR = 1.83 for risk drinking), while lack of the ADH1C rs698 protective allele was significantly associated with AUD-related phenotypes (OR = 2.32 for AUD).