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The effects of childhood adversity on problem drinking

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 , 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 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 in European-American men.

Results will be published in the December 2014 online-only issue of Alcoholism: Clinical & 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 . “Rather than hypothesizing about ‘genetic susceptibility,’ we now have identified over 30 different genes that are associated with 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.