Defining nicotine dependence for genetic research: evidence from Australian twins

Abstract

Background. Whether current criteria used to define nicotine dependence are informative for genetic research is an important empirical question. The authors used items of the DSM-IV and of the Heaviness of Smoking Index to characterize the nicotine dependence phenotype and to identify salient symptoms in a genetically informative community sample of Australian young adult female and male twins.Method. Phenotypic and genetic factor analyses were performed on nine dependence symptoms (the seven DSM-IV substance dependence criteria and the two Heaviness of Smoking Index (HSI) items derived from the Fagerstro¨m Tolerance Questionnaire, time to first cigarette in the morning and number of cigarettes smoked per day). Phenotypic and genetic analyses were restricted to ever smokers.Results. Phenotypic nicotine dependence symptom covariation was best captured by two factors with a similar pattern of factor loadings for women and men. In genetic factor analysis item covariation was best captured by two genetic but one shared environmental factor for both women and men ; however, item factor loadings differed by gender. All nicotine dependence symptoms were substantially heritable, except for the DSM-IV criterion of 'giving up or reducing important activities in order to smoke ', which was weakly familial.Conclusions. The salient behavioral indices of nicotine dependence are similar for women and men. DSM-IV criteria of tolerance, withdrawal, and experiencing difficulty quitting and HSI items time to first cigarette in the morning and number of cigarettes smoked per day may represent the most highly heritable symptoms of nicotine dependence for both women and men.

Overview of the pharmacogenomics of cigarette smoking

“…19,21,27 A genetic influence on nicotine withdrawal symptoms and smoking cessation has also been identified with heritability estimated at 26-48 and 50-58%, respectively. [28][29][30] Taken together, these studies suggest a substantial genetic contribution to most aspects of smoking. It should be noted that genetic risk factors for different aspects of smoking (such as initiation and persistence) only partially overlap, suggesting some genes will be specific to one smoking phenotype whereas others may influence multiple aspects of smoking.…”

α-5/α-3 nicotinic receptor subunit alleles increase risk for heavy smoking

“…CPD was selected as the single phenotype for analysis, because it is a highly heritable, 3 widely used phenotype in genetic studies of smoking. 7,8,10 To understand the relationship between CPD and DSM-IV ND, we analyzed an epidemiologic dataset, the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC 11 ).…”

“…The twin studies suggest that a majority of risk for nicotine dependence (ND) may be attributable to genetic factors. More recent twin smoking research [3][4][5] suggests that the heritability of ND is even higher.…”

“…Lessov et al 3 analyzed multiple ND-related phenotypes in a large twin study. They concluded that the cigarettes per day (CPD) variable has one of the highest genetic loadings among ND-related phenotypes.…”

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background

“…Twin and family studies have suggested a high heritability (56-75%) for ND; [3][4][5][6][7] clearly, social, psychological and other environmental factors as well as comorbidities, such as alcohol use and depression, contribute as well. 8,9 Several genome-wide scans have been performed suggesting loci linked to smoking behavior and ND.…”