Susceptibility genes for nicotine dependence: a genome scan and follow-up in an independent sample suggest that regions on chromosomes 2, 4, 10, 16, 17 and 18 merit further study.
Cigarette smoking is associated with considerable morbidity, mortality, and public health costs. Genetic factors have been conclusively show to influence both smoking initiation and nicotine dependence, but none of the genes involved have yet been conclusively identified. A genome scan was conducted to identify chromosomal regions linked to nicotine dependence in a collection of 130 families containing 308 nicotine dependent individuals from Christchurch, New Zealand. The best evidence for linkage was found with a marker on chromosome two which resulted in a heterogeneity LOD score of 2.63.
To identify regions that warranted further study, we compared them to an empirical baseline, and found modest evidence for linkage on chromosomes 2, 4, 10, 16, 17 and 18. These were investigated by additional genotyping of the Christchurch sample and by examination in an independent sample from Richmond, Virginia (91 families with 211 nicotine dependent individuals).
Analysis of the Richmond provided limited additional evidence for linkage, particularly in regions on chromosomes 2, 10, 16, 17 and 18. The sample sizes used here provide only limited power to detect linkage for a genetically complex trait such as nicotine dependence. Therefore, some or all of the most positive results could be due to chance. However, the evidence for limited replication in several regions across the two samples suggests that some of these regions may contain genes influencing nicotine dependence and therefore deserve further study.