Heavy Smoking May Be a Genetic Thing

Patients who start smoking at a younger age appear to have a genetic susceptibility to heavy smoking as adults, researchers found. In a meta-analysis, smokers who started at age 16 or younger and had at least one mutation in a nonsynonymous single-nucleotide polymorphism in CHRNA5 -- rs16969968 -- had a significantly greater risk for heavy smoking in adulthood than those who started smoking later (OR 1.45, 95% CI 1.36 to 1.55, P=0.01), according to Laura Bierut, MD, of Washington University School of Medicine in St. Louis, Mo., and colleagues.

"The finding of a stronger genetic risk in early-onset smokers supports public health interventions to reduce adolescent smoking," they wrote in the Aug. 6 issue of Archives of General Psychiatry. The results are supported by earlier studies in animal models showing that "the developing adolescent brain [is] particularly vulnerable to addictive effects of nicotine and by human studies suggesting that adolescent neurodevelopment is a particularly vulnerable period for the development of addiction," the authors explained.

The researchers analyzed a sample of 33,348 ever-smokers from 43 studies and stratified participants into early-onset -- those who started smoking at 16 or younger -- and late-onset smokers or those who started after age 16. Additionally, participants had presence of the rs16969968 genotype, or an analogous SNP called rs1051730, measured against heavy and light smoking status. The analogous gene was included, the authors wrote, because it provided "statistically equivalent results and there is biological evidence that rs16969968 alters receptor function."

"An unresolved issue is whether rs16969968 plays a role in the heightened susceptibility to nicotine dependence in early-onset smokers," they added. Heavy smoking status was defined as more than 20 cigarettes per day, while light smoking was defined as 10 or fewer cigarettes per day, with moderate smoking status excluded from the analysis. They found that the overall risk for heavy smoking in participants who initiated smoking early was significant at an odds ratio of 2.63 (95% CI 2.49 to 2.78, P