UCSF Researchers Shed Light on Genetic Factors Behind Alcohol Dependence

Understanding the genetic factors behind alcohol dependence — and using that information to improve treatment — has been the goal of many scientific studies. Now, a group of UCSF researchers has moved one step closer to unraveling what one called the “complicated web” of components that determine an individual’s response to alcohol and likelihood to abuse it. In a recently published study, scientists from UCSF’s Ernest Gallo Clinic and Research Center took 367 white siblings with a family history of alcohol abuse and had each consume three alcoholic drinks over a 10-minute period at 10 a.m. To measure the alcohol’s effects, researchers observed participants’ body swaying and also asked them for a self-report of their emotional and physical feelings after consuming the drinks. “We wanted to see if there was a range of [alcohol] responses, and indeed there was,” said Raymond L. White, PhD, director of the Gallo Center and the senior author of the study, which appeared in the Dec. 8 online edition of the Proceedings of the National Academy of Sciences. Response to alcohol intake is an important predictor of future alcohol abuse, White said, noting that those who can drink more before feeling intoxicated are more likely to consume in excess and become dependent. Notably, the researchers found a significant link between an individual’s level of alcohol response and whether or not he or she possessed a certain DNA sequence variation on chromosome 15. That discovery didn’t come entirely out of left field: In previous studies, that same DNA sequence variation — the single nucleotide polymorphism RS1051730 — has been associated with nicotine dependence and lung cancer. “We already know that smoking and alcohol use are linked, so we were following the leads from those [earlier] smoking studies,” White said. In addition, other studies have connected chromosome 15 to specific types of alcoholism. But until the UCSF study, researchers had not answered a key question about the genetic factors behind the most common forms of alcohol use disorders: Where are the relevant chromosomes located? “Before now, the findings for the regular, broader range of alcoholism had not really been forthcoming,” White said. However, he acknowledged, many other questions remain. “Of the inherited genetic risk [of alcohol dependence], we’re explaining about 3 percent” with RS1051730, he said. “That means there’s a treasure trove of additional components to be ferreted out. It’s a complicated web.” White and his Gallo colleagues plan to continue their research with the same sibling pairs, he said. And at some point down the line, he hopes their findings will be able to help those who are genetically at risk. “By understanding which portion of our genetic makeup influences our response to alcohol, we can begin to understand what type of treatments might be most successful in helping reduce alcohol use disorders,” White said. The study’s co-authors were Geoff Joslyn, Gerry Brush and Margaret Robertson of the Gallo Center; and Tom L. Smith, Jelger Kalmijn and Marc Schuckit from the University of California, San Diego Department of Psychiatry and the Veterans Affairs San Diego Healthcare System.