The study, published in the December issue of the journal Alcoholism: Clinical & Experimental Research, offers evidence that the interaction between smoking and alcohol consumption may partly be due to overlapping genetic risk factors. The results also provide further confirmation that alcoholism is a complex behavior drawing from both environmental and genetic factors.
"Since we know that people who drink often smoke and that smokers often drink, we thought it reasonable to collect some information about the drinking behavior in these families," said lead study author Dr. Kirk C. Wilhelmsen, associate professor in the departments of genetics and neurology at the University of North Carolina at Chapel Hill's School of Medicine.
He also is a member of the Carolina Center for Genome Sciences, the Bowles Center for Alcohol Studies and the UNC Lineberger Comprehensive Cancer Center.
The research team studied 158 families that had at least two first-degree relatives who had smoked 100 or more cigarettes in their lifetime. These included any combination of parents, siblings and offspring who had smoked.
A detailed questionnaire was used to search for alcohol-related behavioral traits, or phenotypes, shared within each family. Questions concerned the quantity of alcohol consumed, such as the number of alcohol drinks per month for six consecutive months and the number of alcohol of drinks consumed in a typical week and typical day.
DNA from blood samples taken from each family participant was analyzed for particular genetic variations. "We looked for excess chromosome sharing of regions that had genes that affect patterns of drinking behavior," Wilhelmsen said.
The researchers applied linkage analysis, which examines differences, or variants, in the DNA sequences of the chromosomes inherited from one's parents. These gene variants determine, in part, many human characteristics, such as a propensity to drinking behavior, Wilhelmsen said. "And when you see aggregation of behavioral traits in families, it can be due to genetics."
The chromosome regions, or loci, identified in this study with the strongest evidence of genes that appear to affect alcohol consumption were in close proximity to those previously found in other linkage studies looking for loci that may affect drinking behavior.
The authors hypothesize that the identified loci – one locus on chromosome two, and two loci on chromosome four – affect alcohol-use phenotypes that precede alcoholism.
The locus on chromosome four involves a cluster of roughly 200 genes, including some that are involved in alcohol metabolism. But saying there's a propensity for alcoholism behavior based on that chromosome location would not be very predictive, in part because it remains unknown exactly which genes or combination of genes play a role in this behavioral effect, Wilhelmsen said.
"Our work provides evidence that variations in genes in a particular region affect drinking behavior. But the basic goal is not to predict who will or won't become alcoholic. The goal is to try to find the genes that play a role, use them as clues to help us learn more about the biology of the disease and then see if we can use this information to select more effective, individualized therapies."
Co-authors with Wilhelmsen were Dr. Li S-C. Cheng of the City of Hope National Medical Center; Drs. Christina N. Lessov-Schlaggar, Karen S. Hudmon and Huijun Z. Ring of the Center for Health Sciences at SRI International; Dr. Christopher Amos of the University of Texas M.D. Anderson Cancer Center; Dr. Heidi S. Feiler of the Gallo Institute's department of neurology; Drs. Judy A. Andrews, Elizabeth Tildesley and Hyman Hops of the Oregon Research Institute; and Dr. Neal L. Benowitz of the University of California at San Francisco's Division of Pharmacology.
The study was funded by the University of California Tobacco-Related Disease Research Program and the State of California.
Note:
Contact Wilhelmsen at (919) 966-1373 or kirk@med.unc.edu
School of Medicine contact: Les Lang, (919) 843-9687 or llang@med.unc.edu