Educational attainment, smoking initiation and lifetime nicotine dependence among male Vietnam-era twins

Cigarette smoking is clearly associated with factors commonly thought to be environmental in origin, such as socioeconomic status (SES). For example, lifetime daily smoking is overrepresented among individuals in lower socioeconomic strata (Matthews et al., 1989; Winkleby et al., 1990; Adler et al., 1994), as are smoking persistence and failed cessation (Kaprio & Koskenvuo, 1988; Escobedo et al., 1990; Pugh et al., 1991). Twin studies, on the other hand, suggest that smoking initiation and nicotine dependence are each, in part, heritable (Shenassa et al., 2003). In the largest review of these data (Sullivan & Kendler, 1999), Sullivan and Kendler report a heritability of 56% (a2=.56) for smoking initiation, with environmental factors shared by twins and those unique to each individual accounting for 24% (c2=.24) and 20% (e2=.20) of the remaining variance, respectively. Further, smoking persistence, often used as a “proxy measure of nicotine dependence”, is more strongly heritable (a2=.67) and influenced by unique environment (e2=.31) with little or no contribution of shared environment (c2=.02). Familial transmission of nicotine dependence per se (Kendler et al., 1999; True et al., 1999; Lessov et al., 2004; Vink et al., 2005), as well as other proxy measures for nicotine dependence, including heavy smoking (Swan et al., 1997), total number of daily cigarettes (Hettema et al., 1999; Koopmans et al., 1999a) and failed smoking cessation (Xian et al., 2003), also appear to be primarily influenced by genetic and unique environmental effects, with little contribution of shared environmental factors. These differences in liability to smoking initiation and proxy measures of nicotine dependence, as well as nicotine dependence per se, have been confirmed in stage models in which progression of one phenotype is explicitly dependent upon the expression of an earlier phenotype with a potentially distinct liability (Heath et al., 1991; Heath & Martin, 1993; Koopmans et al., 1999a; Madden et al., 1999; Heath et al., 2002; Neale et al., 2006). The differences in the effects of shared environment on smoking initiation versus nicotine dependence suggest that measured environmental factors, such as SES, may be differentially related to smoking initiation, relative to smoking persistence and progression to nicotine dependence. However, measured “environmental” factors often show genetic influence when tested in genetically-informative designs. For example, educational attainment, one of the components of individual socioeconomic status most strongly associated with cigarette smoking, is often heritable when examined in twin studies (Heath & Berg, 1985). Thus, it is also possible that the association between socioeconomic indicators and smoking outcomes reflects gene — environment correlation, such that common genetic factors contribute to both SES and liability to smoking, or gene x environment interaction, as indicated by changes in the magnitude of the heritability of smoking initiation or nicotine dependence at various levels of SES. Twin studies provide a unique opportunity to examine evidence for gene-environmental correlation and gene x environment interaction. Here, we employ twin structural equation models of gene — measured environment (educational attainment) correlation and gene x measured environment interaction to test whether: 1) educational attainment is more strongly associated with smoking initiation relative to nicotine dependence; 2) common environmental factors shared across twins predict both educational attainment and smoking initiation (shared environment — measured environment correlation); 3) common genetic factors predict both educational attainment and smoking initiation (gene — measured environment correlation); and 4) educational attainment modifies the heritability of smoking initiation and nicotine dependence (gene x education interaction). To our knowledge, this is the first study proposing to examine an indicator of socioeconomic status, educational attainment, and cigarette smoking in the context of a twin design.