Replication of genetic association increases the validity of a finding. Independent replication using nicotine dependence and correlated phenotypes (light versus heavy smokers or cigarettes per day) has been reported repeatedly for rs16969968, either through direct testing or by examining other highly correlated genetic variants [14-19]. Association of this locus for early-onset smokers has also been reported [20]. Community based samples, lung cancer patients, and alcohol dependent subjects all show this same genetic association with smoking behavior and nicotine dependence. Further analysis of the chromosome 15 region identifies at least two statistically distinct variants that contribute to nicotine dependence [12-14, 16, 20].
