Multi-Polygenic Analysis of Nicotine Dependence in Individuals of European Ancestry.

INTRODUCTION: Heritability estimates of nicotine dependence (ND) range from 40% to 70%, but discovery GWAS of ND are underpowered and have limited predictive utility. In this work, we leverage genetically correlated traits and diseases to increase the accuracy of polygenic risk prediction. METHODS: We employed a multi-trait model using summary statistic-based best linear unbiased predictors (SBLUP) of genetic correlates of DSM-IV diagnosis of ND in 6394 individuals of European Ancestry (prevalence = 45.3%, %female = 46.8%, µâ€Šage = 40.08 [s.d. = 10.43]) and 3061 individuals from a nationally-representative sample with Fagerström Test for Nicotine Dependence symptom count (FTND; 51.32% female, mean age = 28.9 [s.d. = 1.70]). Polygenic predictors were derived from GWASs known to be phenotypically and genetically correlated with ND (i.e., Cigarettes per Day [CPD], the Alcohol Use Disorders Identification Test [AUDIT-Consumption and AUDIT-Problems], Neuroticism, Depression, Schizophrenia, Educational Attainment, Body Mass Index [BMI], and Self-Perceived Risk-Taking); including Height as a negative control. Analyses controlled for age, gender, study site, and the first 10 ancestral principal components. RESULTS: The multi-trait model accounted for 3.6% of the total trait variance in DSM-IV ND. Educational Attainment (ß = -0.125; 95% CI: [-0.149,-0.101]), CPD (0.071 [0.047,0.095]), and Self-Perceived Risk-Taking (0.051 [0.026,0.075]) were the most robust predictors. PGS effects on FTND were limited. CONCLUSIONS: Risk for ND is not only polygenic, but also pleiotropic. Polygenic effects on ND that are accessible by these traits are limited in size and act additively to explain risk. IMPLICATIONS: These findings enhance our understanding of inherited genetic factors for nicotine dependence. The data show that genome-wide association study (GWAS) findings across pre- and comorbid conditions of smoking are differentially associated with nicotine dependence and that when combined explain significantly more trait variance. These findings underscore the utility of multivariate approaches to understand the validity of polygenic scores for nicotine dependence, especially as the power of GWAS of broadly-defined smoking behaviors increases. Realizing the potential of GWAS to inform complex smoking behaviors will require similar theory-driven models that reflect the myriad of mechanisms that drive individual differences.

Examining the differential effects of latent impulsivity factors on substance use outcomes in African American men.

African Americans have elevated substance use-related problems during adulthood despite initiating use later than individuals of other racial/ethnic backgrounds. The present study first validated the structure of the UPPS-P Impulsive Behavior Scale and then examined impulsivity as a prospective risk factor for future alcohol, cannabis, and tobacco use, as well as generalized substance problems, in African American men. Data were drawn from the African-American Men's Project, which recruited participants (NWAVE-1 = 504; Mean ageWAVE-1 = 20.7; NWAVE-3 = 379; Mean ageWAVE-3 = 23.6) from rural counties of Georgia. Participants responded to an adapted version of the UPPS-P at Wave 1. Confirmatory factor analyses determined that a 5-factor model of impulsivity and a 3-factor hierarchical model of impulsivity described the data equally well, in comparison to 1-factor, 4-factor, or bifactor models. This supports that the structure of the abbreviated UPPS-P in African Americans is likely consistent with observations in White, Hispanic/Latino, and admixed samples. Notably, all second-order factors of the UPPS-P are not alike in predicting substance use outcomes when examined jointly in African American men. Only Deficits in Conscientiousness, which is a second-order factor comprised of Lack of Premeditation and Lack of Perseverance, affected whether individuals met any criteria for future substance use problems. Our findings provide novel insight into the relationship between impulsivity and substance involvement during emerging adulthood in African American men.

Sex differences in affect-triggered lapses during smoking cessation: A daily diary study.

INTRODUCTION: Smoking lapses during a cessation attempt are common and are thought to be a key predictor of full relapse. Positive and negative affective states have been hypothesized as important precipitants of lapses during quit attempts, although findings have been mixed. Accumulating evidence suggests that women may smoke more when experiencing negative affective states, while men may smoke more when experiencing positive affective states. The possibility that these sex differences may play a role in predicting lapses during a smoking cessation attempt, however, has not been well-investigated. In this study, we hypothesized that, during a quit attempt, negative affect would be more strongly associated with lapses among women, and positive affect would be more strongly associated with lapses among men. METHOD: We conducted a prospective study in which male and female nicotine-dependent smokers (n = 60) made an unaided, 'cold-turkey' quit attempt. For fourteen days following the initiation of the quit attempt, participants completed daily diaries in which they recorded the degree to which states of 'good mood' and 'bad mood' preceded smoking lapses. RESULTS: Consistent with the study hypothesis, findings indicated that men reported higher good-mood-induced smoking lapses than women across the 14-day study interval. Conversely, while levels of bad-mood-induced smoking subsided over the 14-day interval among men, levels persisted among women. DISCUSSION: Results further underscore the need to address sex-specific affective triggers when developing smoking cessation strategies.

Can attitudes about smoking impact cigarette cravings?

Cigarette cravings, especially those in response to environmental stressors and other smoking-related triggers (e.g., passing by a favorite smoking spot), are important contributors to smoking behavior and relapse. Previous studies have demonstrated significant individual differences in such cravings. This study explores the possibility that attitudes about smoking can influence the experience of cigarette craving. Consistent with classical theories of the links between cognition and motivation, we predicted that smokers who exhibit more favorable attitudes towards smoking would have greater cravings. Daily smokers (n=103, mean age=41.8years, 33% female) were instructed to imagine smoking, stress, and neutral scenarios. Cravings were measured prior to and after each exposure. Participants also completed an abridged version of the Smoking Consequence Questionnaire (SCQ) that had them rate the: 1) desirability and 2) likelihood, for eighteen separate negative smoking consequences (e.g., "The more I smoke, the more I risk my health", "People will think less of me if they see me smoking"). Findings revealed that favorable attitudes about the consequences of smoking, as measured by the SCQ-desirability index, significantly predicted cigarette cravings. Findings suggest that individual attitudes toward smoking may play an important role in better understanding cigarette cravings, which may ultimately help identify targets for more efficient and effective cognitive/attitude-based interventions for smoking cessation.