Given that smoking remains the single most important cause of premature mortality – the source of 443,000 deaths per year during 2000 to 2004 in the United States (Adhikari et al. 2008
) – it has enormous importance for understanding the levels and patterns of population mortality (Rogers et al. 2005
). Smoking contributes to mortality differences across cohorts (Preston and Wang 2006
), nations (Pampel 2002
), and socioeconomic groups (Jha et al. 2006
). Such influences will not disappear soon. The decline in regular smoking incidence caused large changes in the relative size of the smoking population, but the rate of decline has slowed more recently (Mendez and Warner 2004
). Indeed, the United States appears to be only halfway to the goal of eliminating this public health hazard (Fiore and Baker 2009
). Along with raising public health concerns, the frustratingly slow progress presents a puzzle about population health and longevity: Despite widespread acceptance of the harm of smoking, high cigarette prices, social disapproval, restrictions on places to light up, and strong desires among users to quit, nearly one fifth of the American adult population still smokes (Thorne et al. 2008
The demographic attention to the composition of populations at risk may provide some insight into these trends, particularly into the difficulties of getting smokers to quit. Although entry into smoking draws from the general population, exit from smoking draws from a continuously changing population of regular smokers. With declining incidence of smoking, those least committed or likely to become addicted to the habit may now either never start or soon quit, while those most attracted or easily addicted more often take up the habit and have more trouble quitting. As a result, those most reticent to exit from smoking status, whose symptoms of nicotine withdrawal are felt most acutely, may come to make up an increasingly larger portion of the smoking population.
Said differently, the composition of the smoking population with regard to genetic propensities to smoke or become addicted may, in particular, have changed. In general, environmental and genetic factors equally contribute to an individual’s risk of becoming a regular smoker; heritability and environmental influence for regular smoking typically range between .4 and .6 (Carmelli et al. 1992
; Hall, Madden, and Lynskey 2002
; Li et al. 2003
; Sullivan and Kendler 1999
) and numerous candidate genes have been identified (for a review see Munafo et al. 2004
). However, genetic influences on smoking vary considerably across different social environments (Boardman 2009
; Boardman et al. 2008
; Timberlake et al. 2006
). The environmental moderation of genetic factors is anticipated by the gene-by-environment interaction (GxE) paradigm (Eaves, Silberg and Erkanli 2003
; Shanahan and Hofer 2005
), and there is relatively consistent evidence that environments may control or enable genetic tendencies to consume cigarettes. This is particularly true when the “environment” is characterized in broad historical periods that have varied social norms, public policies, and institutional constraints and that influence the degree to which genes differentiate between smokers and non-smokers (e.g., Boardman, Blalock, and Pampel 2010
; Kendler, Thornton, and Pederson 2000
Recent decades clearly reflect changes in norms and constraints on smoking that relate closely to policy (Pampel 2005
). Cigarette consumption increased more than fivefold from 1920 to 1960, leveled off during the mid 1960s, and then consistently declined following the mid 1970s. At the peak around 1966, roughly one-half of men and one-third of women in the United States smoked regularly (Forey, Hamling, and Lee 2009
). The timing of this peak roughly corresponded with first report by the Surgeon General regarding the dangers of smoking in 1964 which ultimately led to the Federal Cigarette Labeling and Advertising Act of 1965. This required that all cigarette packages contain a printed copy of the statement: “Caution: Cigarette Smoking May Be Hazardous to Your Health.” Although the scientific community had declared that smoking was unequivocally hazardous to one’s health, it was not until the mid 1970s until formal restrictions were placed on smoking behaviors. In 1973, Arizona became the first state to pass a comprehensive law that limited smoking in public places. More restrictive sets of laws followed, including the 1975 Minnesota Clean Indoor Air Act, which required restaurants to have nonsmoking sections. Twelve years later Aspen, Colorado, became the first city to formally ban all cigarette smoking in restaurants. The push for bans in all restaurants was bolstered by the nineteenth Surgeon General’s Report (USDHHS 1986
), which argued that the “simple separation of smokers and nonsmokers within the same airspace may reduce but cannot eliminate nonsmoker exposure to environmental tobacco smoke.” By the end of 2007, the number of states requiring restaurants to be smoke-free increased to 21 and the number of states without smoking restrictions for restaurants decreased from 19 to 9 (Tynan, Babb, and MacNeil 2008
). The implementation of anti-smoking policies coincided with steady movement toward the acceptance of the harm to health of smoking and rejection of the habit by opinion leaders and large parts of the population.
As others have shown (Boardman et al. 2010
), this historical context provides a critical backdrop for understanding the genetics of smoking and the often-overlooked gene-environment interaction. As both prevalence and incidence have declined in recent years, smokers who continue in the face of external pressures, social sanctions, and anti-tobacco policies have become a more select group. The change thus raises two questions: Has the impact of genetic characteristics on the likelihood of being in the smoking population across the changed over time? And if so, have changes in the smoking environment reduced or heightened genetic influences on this behavior? Answering these questions can shed light on the nature of gene-environment interactions.
The current study extends this period-moderation perspective by examining smoking desistance as the phenotype. Researchers report heritability estimates of successful quitting to be in the range of .3 to .5 (Xian et al. 2003
), but no existing work has examined period effects on the genetics of smoking desistance. Genes implicated in smoking onset are quite different from those associated with smoking desistance (Broms et al. 2006
), and we suspect the period effects on the genetics of smoking desistance may differ as well.
Gene-Environment Interplay and Smoking
Two competing gene-environment interaction models speak to changes in the smoking environment and the genetics of smoking. The social control
model hypothesizes that normative and institutional controls restrict individual behavior, and as a result, two individuals within highly controlled environments may behave similarly despite genetic differences. In this case, phenotypic similarity is simply a function of the social controls linked to laws and legal enforcement, moral codes, religious control, highly organized educational settings, or broad forms of stratification that limit particular individuals’ mobility. For example, Timberlake et al. (2006)
show that religious participation reduces the additive genetic influences on smoking onset among adolescents; their estimated 60% heritability nearly drops to zero for those who report that religion is “more important than anything else.” Economic incentives are equally powerful; Boardman (2009)
shows that states with higher excise taxes per pack of cigarettes have the lowest observed heritability of regular smoking. Again, the taxes serve as an instrument of social control which ultimately dampens genetic influences.
This hypothesis predicts that as anti-smoking pressures intensify and smoking becomes less common, genetic influences on smoking weaken. Early warnings and publicity in the 1960s about the harm of smoking led those with weaker genetic propensities to avoid starting to smoke or to quit soon, leaving those with stronger genetic propensities to begin and continue smoking. This initial change in the population of smokers created strong genetic influence on quitting. In more recent decades, however, the anti-smoking environment and associated disincentives have become strong enough to affect those with genetic propensities. Reduced entrance into smoking and higher quitting among hardcore smokers tends to reduce the predominance of genetically prone smokers in the smoking population and moderate genetic influences.
Alternatively, the social push
model (Raine 2002
) hypothesizes that public policies can actually highlight genetic influences by minimizing “noise” that has the potential to overwhelm and hide genetic expression. According to this model, genetic associations are most clearly observable in benign environments lacking social factors that encourage genetically influenced addictive behaviors. When social noise is minimized by policies or other anti-smoking influences, it allows for “biology to shine through” (Raine 2002
:14). Conversely, when social factors “push” certain behaviors, biological factors become harder to identify. Therefore, as social forces emerge that discourage smoking or remove the positive reinforcement of smoking, it reduces social influences or non-genetic noise and increases the salience of genetic influences.
According to the social push model, the implementation of increasingly restrictive anti-tobacco policies and the acceptance of anti-smoking norms should do more to concentrate smoking among those with genetic vulnerabilities to smoking. Rather than most benefitting those with physiological and genetic traits that increase nicotine addiction (as posited by the social control hypothesis), recent changes may help other types of smokers the most. As a result, those with genetic propensities toward addiction, those who are most easily induced to start smoking and have the most difficulty in quitting, tend to become concentrated in the smoking population. This changing composition of the population at risk increases the salience of genetic influences.
Historical Context as “Environment”
The gene-environment perspective has been extended to include macro events measured by historical periods as structuring the genetics of smoking behaviors. Kendler et al. (2000)
demonstrate that the heritability for tobacco use changes predictably over time. While heritability estimates for men were relatively consistent across the three cohorts born between 1910-1924, 1925-1939, and 1940-1958 (h2
~.60), none of the variance in tobacco use was due to genetic factors in the first cohort of women, but by the third cohort, there were no gender differences in the heritability estimates. They argue that women’s smoking behaviors were highly controlled during the first cohort, but absent these controls, genetic tendencies to use tobacco emerged.
Boardman et al. (2010)
estimate additive genetic influences on having been a regular smoker at one time among U.S. adults born between 1920 and 1970 and show that the genetic influences on regular smoking reached a minimum (h2
~ .05) at the same time as the peak of smoking in the United States (roughly 1964). However, genetic influences on regular smoking increased sharply until the mid 1970s and then declined again to levels reported by other studies. Boardman et al. (2010)
argue that the first change (after the minimum in 1964) was due to the first Surgeon General’s Report regarding the dangers of smoking. That is, a non-causal social push mechanism was in place in which genetic resilience facilitated the relatively easy avoidance of smoking by some, but genetic vulnerability made it more difficult for certain people to avoid smoking and genetic factors thus came to more heavily influence regular smoking. This changed in the mid 1970s when the first legislation came on board to limit the places where people could smoke and to increase taxes on cigarettes. These real controls, they argue, had a causal influence on the genetics of smoking at this time.
In this study, our goal is to extend the notion that historical trends may influence genetic influence by examining a more specific smoking phenotype, smoking desistance. Previous studies focused on having ever been a regular smoker among all adults (Boardman et al. 2010
; Kendler et al. 2000
), while this study focuses on quitting among adults who became regular smokers. If the composition of smokers changes over time, the influence of genetic factors on quitting among the differentially selected group may well change and do so in ways that moderate genetic influences (according to the social control hypothesis) or that strengthen genetic influences (according to the social push hypothesis).
No study has yet to explore macro-level historical changes on the genetic determination of desistance or the transition from regular smoker to non-smoker. We argue that smoking desistance denotes a stronger test of the social control vs. the social push model when the environment is characterized as a time period. If the social and institutional controls related to smoking desistance increased significantly starting in 1973, then the social control model would anticipate that the genetic influences on smoking desistance would decrease after this point. However, the social push model suggests that these forces would have a greater influence on the less genetically vulnerable, leaving the composition of smokers to be more influenced by genetic factors. Hence, following 1973, the genetic influences on smoking desistance should increase. The goal of this paper is to evaluate the relevance of these competing perspectives as related to this important behavior during this critical point in time.