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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%, µâage = 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.
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Alcoholismo , Tabaquismo , Adulto , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Herencia Multifactorial/genética , Fumar , Tabaquismo/diagnóstico , Tabaquismo/epidemiología , Tabaquismo/genéticaRESUMEN
OBJECTIVE: Alcohol minimum unit pricing (MUP) policies establish a floor price beneath which alcohol cannot be sold. The potential effectiveness of MUP policies for reducing alcohol-attributable deaths in the United States has not been quantitatively assessed. Therefore, this study estimated the effects of two hypothetical distilled spirits MUP policies on alcohol sales, consumption, and alcohol-attributable deaths in one state. METHOD: The International Model of Alcohol Harms and Policies tool was used to estimate the effects of two hypothetical MUP per standard drink policies (40-cent and 45-cent) pertaining to distilled spirits products at off-premises alcohol outlets in Michigan during 2020. Prevalence estimates on drinking patterns among Michigan adults were calculated by sex and age group. Prices per standard drink and sales of 9,747 spirits products were analyzed using National Alcohol Beverage Control Association data. Analyses accounted for other alcoholic beverage type sales using cross-price elasticities. RESULTS: Increasing the MUP of the 3.5% of spirits with the lowest prices per standard drink to 40 cents could reduce total alcohol per capita consumption in Michigan by 2.6% and prevent 232 (5.3%) alcohol-attributable deaths annually. A 45-cent MUP would affect 8.0% of the spirits and reduce total alcohol per capita consumption by 3.9%, preventing 354 (8.1%) deaths. CONCLUSIONS: Modestly increasing the prices of the lowest-priced spirits with an MUP policy in a single state could save hundreds of lives annually. This suggests that alcohol MUP policies could be an effective strategy for improving public health in the United States, consistent with the World Health Organization's recommendation.
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Consumo de Bebidas Alcohólicas , Política Pública , Adulto , Humanos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/prevención & control , Etanol , Comercio , Costos y Análisis de CostoRESUMEN
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.
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Negro o Afroamericano , Trastornos Relacionados con Sustancias , Adulto , Georgia , Humanos , Conducta Impulsiva , Masculino , Estudios Prospectivos , Trastornos Relacionados con Sustancias/epidemiología , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Cannabis use (CU) is an etiologically complex behavior with several social, temperamental, neurocognitive, and behavioral precursors. Biometrical and molecular studies suggest an interplay of environmental and pleiotropic influences. However, it remains unclear whether identified genetic effects related to behavioral and temperamental characteristics have developmentally direct or indirect mechanisms on CU behavior. The Transmissible Liability Index (TLI) is a measure of continuous liability based on developmental precursors of substance use disorders. This study aimed to examine if the TLI plays a role in understanding genetic risk for CU behaviors. DESIGN: Genome-wide association studies (n > 10 000; European Ancestry [EA]) of CU, risk tolerance, neuroticism, anxiety, and depression were used to construct polygenic scores (PGSs). Analyses assessed whether PGSs indirectly impacted risk for repeated use via TLI. SETTING: United States of America. PARTICIPANTS: From Add Health study, 4077 individuals of EA age 11 to 21 during baseline interview collection. MEASUREMENTS: Outcomes were initiation and repeated cannabis use (>5× in lifetime). The TLI was parameterized using a latent factor from 21 questions assessing for precursors of disordered use. FINDINGS: The marker-based heritability of TLI, initiation, and repeated use were significant, but modest (14%, P = 0.033; 15%, P = 0.025; and 17%, P = 0.008, respectively). TLI and repeated use were genetically correlated (rg = 0.76, P = 0.033). The PGS for CU was associated with increased risk for repeated use and PGS for risk tolerance and depression were associated with TLI. Mediation analyses indicated significant, but very weak, indirect effects of PGS for risk tolerance and depression on repeated CU via the TLI. CONCLUSIONS: Adolescent behavioral and temperamental characteristics (i.e. the Transmissible Liability Index) appear to be early indicators of repeated cannabis use in adulthood. Although polygenic scores for cannabis use directly increased risk for repeated cannabis use, weak evidence was found for the role of polygenic scores of other internalizing/externalizing traits acting through adolescent derived Transmissible Liability Index on cannabis use behavior.
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Cannabis , Adolescente , Adulto , Trastornos de Ansiedad , Niño , Estudio de Asociación del Genoma Completo , Humanos , Herencia Multifactorial/genética , Factores de Riesgo , Adulto JovenRESUMEN
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.
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Fumar Cigarrillos/epidemiología , Ansia , Conocimientos, Actitudes y Práctica en Salud , Cese del Hábito de Fumar/psicología , Adulto , Comorbilidad , Señales (Psicología) , Femenino , Humanos , Masculino , Ciudad de Nueva York , Encuestas y CuestionariosRESUMEN
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 (nâ¯=â¯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.
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Afecto , Cese del Hábito de Fumar , Fumar/terapia , Tabaquismo/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Factores SexualesRESUMEN
Many studies have provided evidence for the existence of universal constraints on color categorization or naming in various languages, but the biological basis of these constraints is unknown. A recent study of the pattern of color categorization across numerous languages has suggested that these patterns tend to avoid straddling a region in color space at or near the border between the English composite categories of "warm" and "cool". This fault line in color space represents a fundamental constraint on color naming. Here we report that the two-way categorization along the fault line is correlated with the sign of the L- versus M-cone contrast of a stimulus color. Moreover, we found that the sign of the L-M cone contrast also accounted for the two-way clustering of the spatially distributed neural responses in small regions of the macaque primary visual cortex, visualized with optical imaging. These small regions correspond to the hue maps, where our previous study found a spatially organized representation of stimulus hue. Altogether, these results establish a direct link between a universal constraint on color naming and the cone-specific information that is represented in the primate early visual system.