This study explored the prevalence and heritability of smoking initiation in two birth cohorts of young adults (18-25 years) and tested for Genotype × Environment interaction by estimating heritability conditional on birth cohort. The first cohort was born in 1968-1977 and their smoking behavior was assessed in 1993-1995. The prevalence of smoking was 50.9% in men and 39.5% in women. The second cohort was born in 1984-1992 and participated in the longitudinal survey study of the Netherlands Twin Register in 2009-2010. In this cohort a substantially lower prevalence of smoking was seen in both sexes with a prevalence of 22.8% in men and 22.4% in women. Thus, significantly more young adults started smoking in 1993-1995 compared to subjects of the same age in 2009-2010. Those results probably reflect the change in smoking policy in the Netherlands, indicating that the discouragement of smoking is successful. The observed decrease is in line with other studies in the Netherlands (a decrease of smoking from 38% to 30% for man and from 30% to 26% for women, from 1991 to 2009, http://www.stivoro.nl) suggesting that the NTR sample is representative for the Dutch population. A decrease in the prevalence of smoking is also seen in other European countries (a decrease in prevalence in Swiss and Finnish men [2, 3]) and in the United States (a decline of smoking initiation among high school students ).
We evaluated the genetic architecture of smoking in both cohorts and did not find changes in the heritability as a function of environmental exposure. There are different theories to explain GxE interaction mechanisms. Policies and rules with respect to smoking behavior have changed between 1993-1995 and 2009-2010. This changed the general attitude from smoking as acceptable behavior to antismoking (= social push), and could increase heritability since only genetic vulnerable subjects still smoke. On the other hand, when smoking is stigmatized and banned in public places, social forces affect smoking among most persons, both with and without genetic tendencies to smoke (= social control). These social controls will cause an actual drop in smoking among genetically motivated smokers and will decrease the genetic influence on smoking . The fact that we did not observe any changes in the heritability of smoking between both cohorts suggests either that those two mechanisms (social control and social push) counterbalance each other or that there are no GxE interactions for smoking in this age group.
In a Swedish study, regular tobacco use was explored in 3 different birth cohorts: 1910-1924, 1925-1939, 1940-1958. For men, the prevalence (65%, 66%, 72%) and the heritability estimates (53%, 58%, 51%) all were stable across the 3 birth cohorts. In contrast, the prevalence in women increased over time, from 18% in 1920-1924 to 52% in 1940-1958. The heritability estimates also increased remarkably from 0% to 64%. Kendler et al. suggested that heritability increased in women because the social restrictions on tobacco use in women became more relaxed over time . The birth cohorts in the Swedish study were much earlier than the cohorts participating in the NTR study. The different outcomes in men and women in the Swedish data are therefore not surprising.
Heath et al (1993) explored data on smoking initiation in three adult twin samples from Australia, Virginia and AARP. Data were broken down into 4 or 5 birth cohorts ranging from 1915-1939 to 1960-1967. Despite a marked change in the proportion of male (not female) respondents who reported ever having smoked, no evidence was found for cohort differences in genetic and environmental effects (no Genotype × Cohort interaction) for either men or women . Those results are in line with the present study. Heath et al. suggest that the same variables, like personality traits of biological effects, have continued to determine which individuals will become smokers, but that in more recent years only individuals with more extreme values on those traits are becoming smokers.
In the studies of Kendler et al and Heath et al, birth cohort and age effects are intertwined. Kendler et al showed that 20% of the total variance in lifetime regular tobacco use was explained by age. In contrast, in our study we analysed data of two groups of twins from different birth cohorts both measured when they were between 18 and 25 years old.
A study from the USA explored the heritability for smoking onset in different states rather than for different birth cohorts (mean age 16.4 years, age range 12-21, n = 2060 twin- and sibling pairs from 31 states) and reported that the average rate of smoking onset varied significantly across states (overall, 45% of the respondents reported smoking onset) but the measure of genetic influence did not. In contrast, the genetic influence for daily smoking varied across states .
Although the samples described in the other studies have different backgrounds compared to ours, the results suggest that the heritability of smoking initiation is not influenced by changes in prevalence ([24, 25] and present study) while for regular/daily smoking the heritability seems to vary with fluctuating prevalence [17, 25].
Boardman suggested that genes for smoking initiation may be different from those associated with daily smoking. Initiation of smoking might be more heavily influenced by personality characteristics such as novelty seeking or impulsivity, whereas regular tobacco use is related to other mechanisms such as nicotine metabolism. In line with this theory, recent meta-analyses of genome-wide association studies for smoking phenotypes detected significant associations between number of cigarettes smoked per day and polymorphisms in nicotine metabolism genes while those associations were not detected for smoking initiation [26, 27].
We found that the genetic architecture for smoking initiation did not differ as a function of environmental conditions. In the data of the NTR, we also observed a change in the prevalence of alcohol use over the past 15 years (an increase). The heritability for alcohol use (alcohol initiation, frequency and quantity) was stable over the cohorts (Geels LM, Bartels M, van Beijsterveldt CEM, van der Aa N, Vink JM, Boomsma DI: Trends in adolescent alcohol use: Effects of age, sex and cohort, submitted). Those results are in line with our results on smoking initiation and suggest that changes in environmental factors causing a change in prevalence not automatically lead to change in the genetic architecture.
Our full genetic model suggested higher heritability estimates for men than for women while shared environmental influences were higher in women than men. A formal test showed that a model without sex differences did not worsen the fit of the model significantly, based on a p-value threshold of 0.01 but this test was borderline significant (p = 0.0195). Other studies exploring sex differences in genetic architecture showed contrasting results. A Finnish study on smoking initiation (early, late, never) reports a higher influence of genetic factors in men compared to women  while a meta-analysis for smoking initiation (based on 6 studies) showed a higher heritability in women compared to men , suggesting that if sex differences in heritability exist, they probably are not large. We did not find sex-differences in heritability of smoking initiation in an adult NTR sample  with a mean age of 30.5 years. The cohorts in the present study consist of younger adults (18-25) and at this age the contribution of environmental influences could differ for men and women. However, in a previous study of twins registered with the NTR, the predictors of the uptake of smoking were similar in boys and girls .