Genetic risk may contribute to the rapid progression of daily and heavy smoking during adolescence and subsequent problems with nicotine dependence and smoking cessation in adulthood, according to a recent study.
The research may have implications for the development of initiatives that deter smoking in adolescents, reported Daniel W. Belsky, Ph.D., of the University of North Carolina at Chapel Hill and Duke University Medical Center, Durham, N.C., and his associates. The 38-year longitudinal study included 1,037 men and women from the Dunedin Multidisciplinary Health and Development Study of New Zealand. Researchers assessed participants with a multilocus genetic risk score (GRS), originating from three meta-analyses of genome-wide association studies (GWAS) that used the number of cigarettes smoked daily as their phenotype. Dr. Belsky and his team focused their investigation on the single-nucleotide polymorphisms in 15q25.1 and19q13.2 (JAMA Psychiatry 2013 March 27 [doi:10.1001/jamapsychiatry.2013.736]).
Genotyping was possible in 880 Dunedin subjects. In addition to evaluating family history in these individuals, researchers gathered smoking information at eight assessments from the age 11-38 years.
The GRS was not associated with whether or when subjects started smoking. "In fact, daily smokers who did not progress to heavy use were at lower genetic risk than individuals who never smoked," the researchers wrote.
Among 627 ever-smokers in the cohort, those with a higher genetic risk were more likely to rapidly progress to heavy smoking, meaning 20 or more cigarettes daily (hazard ratio, 1.35; 95% confidence interval, 1.14-1.58).
Adolescents with high genetic risk had a greater chance of becoming daily smokers by age 15 (relative risk, 1.24; 95% CI, 1.06-1.45) and progressing to heavy smoking by age 18 (RR, 1.43; 95% CI, 1.10-1.86).
Over the course of the study, subjects with a high genetic risk accumulated more pack-years of smoking. As adults, 27% of ever-smokers became nicotine dependent and those at higher genetic risk had a greater chance of doing so (HR, 1.27; 95% CI, 1.09-1.47). Additionally, of 277 cohort members who smoked daily during their 30s, those with a higher genetic risk were more likely to use smoking to cope with stress.
Further analyses found that smoking cessation was also difficult in adults at high genetic risk. For example, in the cohort of 277 daily smokers, 53% quit smoking a month or longer across 72 months follow-up; however, relapse occurred in 62%. Quitters with a higher genetic risk had a greater chance of relapsing (HR, 1.22; 95% CI, 1.02-1.45).
Only 20% of daily smokers abstained from smoking for a year or more.
Associations detected between the GRS and smoking phenotypes were small, noted the study authors. "Children who our study would classify at high genetic risk are not guaranteed to become addicted if they try smoking, and, even more importantly, children we would classify at low genetic risk are not immune to addiction."
Finally, researchers found that that the GRS score did not correlate with family history. "The GRS contained different information about risk for developmental and mature phenotypes of smoking behavior, compared with family history," reported the study authors.
The authors said that their research "adds a genetic dimension to longstanding arguments" in favor of early cigarette prevention of cigarette consumption, including surtaxes and age restrictions on tobacco purchases.
Funding for this study was provided through grants from various organizations, including the U.S. National Institute on Aging, the U.S. National Institute on Mental Health, and the U.K. Medical Research Council. The Dunedin Multidisciplinary Health and Development Research Unit is supported by the New Zealand Health Research Council.