These findings should be considered in light of three limitations. First, although the Dunedin Study sample consisted of European-descent individuals, as did the samples analyzed in the GWAS used to develop the GRS, we cannot rule out the possibility of population stratification. Further, replication in other populations is needed.59 Second, our analyses of cessation were subject to censored data. The life history calendars ended at the age 38 follow-up and thus the data do not reflect relations with phenotypic events occurring after this age. Also, self-reports of temporally remote events could be inaccurate due to forgetting or other biases. Third, the four-decades of follow-up in the Dunedin Study coincided with major secular events such as bans against smoking in the workplace. Comparisons of cohorts born at different times might elucidate gene-policy interactions in smoking behavior and speak to the generalizability of the current findings.60,61
