While the influence of heritable factors on the development of alcohol use disorders (AUDs) has been documented in family pedigree and twin studies for decades, identification of specific genetic variants that influence AUDs continues to be challenging. The ADH1B gene has consistently been implicated in problem drinking, but rarely incorporated into gene/environment investigations of alcohol phenotypes. A study examining the joint effects of variation in ADH1B and childhood adversity on heaviness of alcohol consumption and AUD symptoms has found that, under conditions of childhood adversity, the genetic variant on the ADH1B allele that typically protects against problem drinking does not exert its protective effects in European-American men.
Results will be published in the December 2014 online-only issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
“We have only scratched the surface in terms of identifying gene variants that influence the development of AUDs,” said Carolyn E. Sartor, assistant professor in the department of psychiatry at Yale University School of Medicine as well as corresponding author for the study. “In view of the complex nature of the disorder and the likelihood that there are dozens of risk variants, we have a long way to go to account for substantial variance in risk for AUD. However, there are numerous variants that have substantial support at this point, implicating several systems, most notably, alcohol metabolism.”
“While we still don’t understand everything, we have come far over the past 20 years in our understanding of the genetic vulnerability of alcoholism.” added Victor Hesselbrock, professor of psychiatry at the University of Connecticut School of Medicine. “Rather than hypothesizing about ‘genetic susceptibility,’ we now have identified over 30 different genes that are associated with alcohol dependence and its clinical features. Some of the findings were expected and relate to ethanol metabolism or central nervous system functioning. Other findings were less expected and relate to other biological systems such as the perception of taste. Many of these findings have contributed to our better understanding of the etiology and the sequela of chronic heavy drinking, including AUDs.”
Sartor and her colleagues analyzed data drawn from a multi-site study of the genetics of alcohol, cocaine, and opioid dependence. The sample for this study comprised 2,617 African-American (AA) and 1,436 European-American (EA) participants. In both AA and EA subsamples, women accounted for just less than half of the subjects, the average age was about 40, and approximately one-third of subjects had completed fewer than 12 years of education. The authors tested the most significant ADH1B single nucleotide polymorphisms (SNPs or DNA sequence variations) for alcohol dependence pulled from a larger genome-wide association study with this sample, ADH1B-rs1229984 (Arg48His) in the EA subsample and ADH1B-rs2066702 (Arg369Cys) in the AA subsample.
An alcohol metabolizing gene called ADH1B is strongly linked to risk for alcohol use disorders (AUDs). The His allele (genetic variant) at ADHD1B-rs1229984 is considered protective against AUDs. Experiencing adverse events during childhood, such as physical or sexual abuse or witnessing violence, is a well-documented risk factor for alcohol problems. A study of the effects of both the ADH1B gene and childhood adversity has found that under conditions of childhood adversity, the ADH1B His allele does not exert its protective effects against problem drinking in European-American men.
Yale University School of Medicine
University of Connecticut School of Medicine