The Concept of Resistance to Substance Use and a Research Approach: The Resist! Project.

Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders.

Effects of family history of alcohol problems on alcohol consumption: Stronger for medically underserved men.

Family history (FH), informed by genetics and family environment, can be used by practitioners for risk prediction. This study compares the associations of FH with alcohol outcomes for medically underserved (MUS) men and women with the associations for non-underserved individuals to assess the utility of FH as a screening tool for this high-priority group. Data were from 29,993 adult lifetime drinkers in the Wave 1 (2001-2002) and Wave 2 (2004-2005) National Epidemiologic Survey on Alcohol and Related Conditions. All variables except FH were measured at Wave 2. Dependent variables were 12-month alcohol consumption and alcohol use disorder (AUD). FH scores (FH-SCORE) measured the proportion of first- and second-degree biological relatives with alcohol problems. MUS status was defined by household income at or below 100% of the federal poverty line and participants reporting no usual source of health care. Multivariate linear and logistic regression models tested main and interaction effects. Models showed a significant interaction of FH-SCORE with MUS status (p < .01), with a stronger effect of FH on alcohol consumption for the MUS group. This moderating effect was weaker for women than for men (FH-SCORE x MUS x Sex three-way interaction: p < .01). AUD models showed a significant positive association with FH-SCORE (p < .001) but no association with MUS status and no significant interaction effects. In this sample of lifetime drinkers, FH was associated with higher alcohol consumption, especially for MUS men. These results encourage additional validation of FH scores to prioritize MUS adults at high risk for alcohol problems to receive preventive interventions.

The Association Between Health Literacy and Tobacco Use: Results from a Nationally Representative Survey.

Dual use of conventional cigarettes and electronic cigarettes presents an emerging public health issue. Previous research has demonstrated a negative relationship between health literacy and conventional cigarette (CIG) use. However, the relationship between health literacy and e-cigarette (ECIG) use remains unclear. This studies examines the possible association of health literacy and CIG, ECIG, or dual use. A multinomial regression was used to model the association between health literacy and current CIG use, current ECIG use, or dual tobacco use status using state-optional data from the 2016 Behavioral Risk Factor Surveillance System (BRFSS; N = 40,404). One-third of the sample (N = 13,478; 33.3%) had initiated tobacco use. Approximately 36.6% of participants exclusively used cigarettes. A smaller proportion of participants were dual users of ECIG and CIGs (7.0%) and e-cigarette exclusive users (4.5%). After adjusting for covariates, higher levels of oral health literacy was associated with lower odds of current dual use. However, there was no significant association between written HL and either conventional cigarette use or electronic cigarette use or after adjusting for covariates. Oral messaging around the dangers of CIG use may be effective at lowering odds of CIG or dual use, especially for those with higher levels of HL. Further research is needed to examine how to best disseminate information regarding the health risks of ECIGs.

GW-SEM 2.0: Efficient, Flexible, and Accessible Multivariate GWAS.

Most genome-wide association study (GWAS) analyses test the association between single-nucleotide polymorphisms (SNPs) and a single trait or outcome. While valuable second-step analyses of these associations (e.g., calculating genetic correlations between traits) are common, single-step multivariate analyses of GWAS data are rarely performed. This is unfortunate because multivariate analyses can reveal information which is irrevocably obscured in multi-step analysis. One simple example is the distinction between variance common to a set of measures, and variance specific to each. Neither GWAS of sum- or factor-scores, nor GWAS of the individual measures will deliver a clean picture of loci associated with each measure's specific variance. While multivariate GWAS opens up a broad new landscape of feasible and informative analyses, its adoption has been slow, likely due to the heavy computational demands and difficulties specifying models it requires. Here we describe GW-SEM 2.0, which is designed to simplify model specification and overcome the inherent computational challenges associated with multivariate GWAS. In addition, GW-SEM 2.0 allows users to accurately model ordinal items, which are common in behavioral and psychological research, within a GWAS context. This new release enhances computational efficiency, allows users to select the fit function that is appropriate for their analyses, expands compatibility with standard genomic data formats, and outputs results for seamless reading into other standard post-GWAS processing software. To demonstrate GW-SEM's utility, we conducted (1) a series of GWAS using three substance use frequency items from data in the UK Biobank, (2) a timing study for several predefined GWAS functions, and (3) a Type I Error rate study. Our multivariate GWAS analyses emphasize the utility of GW-SEM for identifying novel patterns of associations that vary considerably between genomic loci for specific substances, highlighting the importance of differentiating between substance-specific use behaviors and polysubstance use. The timing studies demonstrate that the analyses take a reasonable amount of time and show the cost of including additional items. The Type I Error rate study demonstrates that hypothesis tests for genetic associations with latent variable models follow the hypothesized uniform distribution. Taken together, we suggest that GW-SEM may provide substantially deeper insights into the underlying genomic architecture for multivariate behavioral and psychological systems than is currently possible with standard GWAS methods. The current release of GW-SEM 2.0 is available on CRAN (stable release) and GitHub (beta release), and tutorials are available on our github wiki ( https://jpritikin.github.io/gwsem/ ).

The Genetic and Environmental Influences Contributing to the Association between Electronic and Conventional Cigarette Initiation.

INTRODUCTION: As the use of electronic cigarette (EC) continues to rise in the United States, especially among adolescents and young adults, it is necessary to better understand the factors associated with EC initiation. Specifically, it is unclear how genetic and environmental contributions influence the initiation of EC. Furthermore, the degree to which genetic and environmental influences are shared between EC initiation and conventional cigarette (CC) initiation is unknown. METHODS: A sample of young adult twins ages 15-20 (N = 858 individuals; 421 complete twin pairs) was used to estimate the genetic and environmental influences on the liability of initiation unique to EC and CC as well as the degree to which these factors are shared between the two. Approximately 24% of participants initiated the use of EC, 19% initiated the use of CC, and 11% initiated the dual use. RESULTS: Combined contributions of additive genetic and shared environmental influences were significant for CC (ACC = 0.19 [95% confidence interval {CI} = 0-0.79], p = 0.57; CCC = 0.42 [95% CI = 0-0.70], p = 0.13) and EC (AEC = 0.25 [95% CI = 0-0.83, p = 0.44; CEC = 0.42 [95% CI = 0-0.73], p = 0.12), whereas unique environmental influences were significant (ECC = 0.39 [95% CI = 0.18-0.57], p < 0.001; EEC = 0.32 [95% CI = 0.14-0.56], p < 0.001). Results also demonstrated a significant overlap of the unique environmental (rE = 0.87, p < 0.001) and familial influences contributing to correlation between the two phenotypes in the bivariate analysis. CONCLUSIONS: These preliminary results suggest that both genes and environmental influences are potential drivers of EC initiation among adolescents and young adults. IMPLICATIONS: This article is the first to use a sample of twin to estimate the contributions of genetic and environmental influences toward EC initiation and estimate the potential for overlapping influences with CC initiation. This study has implications for future debate about the etiology of EC and CC use with respect to potential overlapping genetic and environmental influences.

Assessing Stakeholder Perceptions of the Utility of Genetic Information for the Clinical Care of Mental Health Disorders: We Have a Will but Need to See the Way.

Academic stakeholders' (primarily mental health researchers and clinicians) practices and attitudes related to the translation of genetic information into mental health care were assessed. A three-part survey was administered at two large, urban universities. Response frequencies were calculated. Participants (N = 64) reported moderate levels of translational practice, adequate levels of genetic knowledge, and variable levels of genetic competence. They held positive attitudes toward translating genetic information about mental health broadly but negative attitudes about the impact that such information would have on specific aspects of care. The current study lays the groundwork for further inquiry into translating genetic information to mental health care.

The Influence of Co-Occurring Substance Use on the Effectiveness of Opiate Treatment Programs According to Intervention Type.

This systematic review describes the influence of co-occurring substance use on the effectiveness of opiate treatment programs. MEDLINE/PubMed, Embase, PsychINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from database inception to November 28, 2018, to identify eligible opioid treatment studies in the United States that assessed the relationship between co-occurring substance use and treatment outcome (i.e., opioid abstinence and treatment retention). A total of 34 eligible studies were included. Overall, co-occurring substance use was associated with negative treatment outcomes regardless of intervention type. However, patterns varied by substance and intervention type. In particular, co-occurring use of cocaine or marijuana with opioids was associated with reduced treatment retention and opioid abstinence regardless of intervention type. Co-occurring use of amphetamines, compared with no use or reduced use of amphetamines, decreased treatment retention. Co-occurring use of alcohol was both positively and negatively associated with treatment outcomes. One study reported a significant positive association between sedative use and opioid abstinence. Generally, findings suggest that combined interventions reported better health outcomes compared with pharmacological or behavioral intervention studies alone. The findings of this review emphasize the need to comprehensively study and address co-occurring substance use to improve opiate treatment programs.

Assessment of Co-Occurring Substance Use During Opiate Treatment Programs in the United States.

The effectiveness of opiate treatment programs (OTPs) can be significantly influenced by co-occurring substance use, yet there are no standardized guidelines for assessing the influence of co-occurring substance use on treatment outcomes. In this review, we aim to provide an overview on the status of the assessment of co-occurring substance use during participation in OTPs in the United States. We searched 4 databases-MEDLINE/PubMed, EMBASE, PsychINFO, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL)-from database inception to November 2018 to select relevant publications on OTPs that assessed participants' co-occurring substance use. We used a standardized protocol to extract study, intervention, and co-occurring substance use characteristics. Methodological quality was assessed using the Quality in Prognosis Studies tool. Of the 3,219 titles screened, 614 abstracts and 191 full-text original publications were assessed, leaving 85 eligible articles. Co-occurring substance use was most often assessed during opioid treatments using combined (pharmacological and behavioral) (n = 57 studies) and pharmacological (n = 25 studies) interventions. Cocaine, alcohol, marijuana, and benzodiazepines were frequently measured, while amphetamines and tobacco were rarely assessed. Great variation existed between studies in the timing and measurement of co-occurring substance use, as well as definitions for substances and polysubstance/polydrug use. Inconsistencies in the investigation of co-occurring substance use make comparison of results across studies challenging. Standardized measures and consensus on research on co-occurring substance use is needed to produce the evidence required to develop personalized treatment programs for persons using multiple substances and to inform best-practice guidelines for addressing polydrug use during participation in OTPs.

Associations Between Initial Subjective Experiences with Tobacco and Self-Reported Recent Use in Young Adulthood.

BACKGROUND: Youth tobacco use behaviors are predictive of patterns in adulthood and effect long-term health outcomes. Yet, few studies have examined the effect of initial subjective experiences (ISEs) during first tobacco use, which has been found to be an indicator of individuals. sensitivity to nicotine and vulnerability to dependence. OBJECTIVE: The present study aimed to determine the prevalence of ISEs across a variety of tobacco products, evaluate the factor structure of ISEs by first tobacco product used, and examine the relationship between ISEs and recent (30-day) use of tobacco products across time, using a university sample. METHODS: Exploratory factor analyses were conducted to identify latent factors present with respect to items measuring ISEs with tobacco, separately by tobacco product (e.g. cigarettes, cigars, hookah, e-cigarettes). Factor scores for positive and negative ISEs were calculated. Multiple logistic regression analyses were conducted to examine associations between ISEs and recent use of each tobacco product, adjusted for age at first use, sex, race/ethnicity, and cohort. RESULTS: ISEs differ by the first tobacco product used. Associations between factor scores for positive and negative ISEs and recent use were found across a variety of tobacco products. Overall, positive ISEs were more strongly associated with recent use, relative to negative ISEs. CONCLUSIONS: Further research is needed to identify genetic and biological pathways and social contexts influencing initial subjective experiences with tobacco use, in efforts to delay the initiation for tobacco use and reduce risk for continued use among young adults.

Assessing the Association Between E-Cigarette Use and Exposure to Social Media in College Students: A Cross-Sectional Study.

BACKGROUND: Social media platforms provide an indirect medium for encouraging e-cigarette use between individuals and also serve as a direct marketing tool from e-cigarette brands to potential users. E-cigarette users share information via social media that often contains product details or health-related claims. OBJECTIVE: Determine whether e-cigarette use is associated with exposure to e-cigarettes on social media in college students. METHODS: Data from a sample of 258 college students was obtained via a clicker-response questionnaire (90% response rate). Demographic, lifetime and current e-cigarette/cigarette use, and e-cigarette exposure via social media (peer posts or advertisements) were examined. Logistic regression was used to assess the relationship between lifetime and current e-cigarette use and viewing peer posts or advertisements on social media while adjusting for cigarette use and self-posting about e-cigarettes. RESULTS: Overall, 46% of participants reported lifetime e-cigarette use, 16% current e-cigarette use, and 7% were current dual users of e-cigarettes and cigarettes. There were positive and significant associations between lifetime e-cigarette use and viewing peer posts (aOR = 3.11; 95% CI = 1.25-7.76) as well as advertisements (aOR = 3.01; 95% CI = 1.19-7.65) on e-cigarettes via social media after adjusting for cigarette use. Current e-cigarette use was only significantly associated with viewing peer posts via social media (aOR = 7.58; 95% CI = 1.66-34.6) after adjusting for cigarette use. Conclusions/Importance: Almost half of college students view peer posts and advertisements on e-cigarettes via social media. This exposure is associated with individual e-cigarette use. Continued efforts to examine online e-cigarette content are needed to help future interventions decrease e-cigarette use.

Comparison of Twin and Extended Pedigree Designs for Obtaining Heritability Estimates.

This study explores power assumptions relating to extended pedigree designs (EPD) and classical twin designs (CTD). We conducted statistical analyses to compare the power of the two designs for examining neuroimaging phenotypes, varying heritability and varying whether shared environmental variance is fixed or free. Results indicated that CTDs have more power to estimate heritability, with the exception of one condition: in EPDs, the power increases relative to CTDs when shared environmental variance contributes to sibling similarity only. We additionally show that assuming a priori that shared environmental effects play no role in a phenotype-as is commonly done in pedigree designs-can lead to substantially biased heritability estimates. General results indicate that both CTDs and EPDs obtain quite precise heritability estimates. Finally, we discuss methodological considerations relating to assumptions about age effects and shared environment.

Genetic and Environmental Influences on Smoking Behavior across Adolescence and Young Adulthood in the Virginia Twin Study of Adolescent Behavioral Development and the Transitions to Substance Abuse Follow-Up.

Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role.

Examining interactions between polygenic scores and interpersonal trauma exposure on alcohol consumption and use disorder in an ancestrally diverse college cohort.

Introduction: Genetic factors impact alcohol consumption and use disorder (AUD), with large-scale genome-wide association studies (GWAS) identifying numerous associated variants. Aggregate genetic methods in combination with important environmental factors (e.g., interpersonal trauma [IPT]) can be applied to expand our understanding of the ways by which genetic and environmental variables work together to influence alcohol consumption and disordered use. The present study aimed to detail the relationships between genome-wide polygenic scores (PGS) for alcohol phenotypes (i.e., alcohol consumption and AUD status) and IPT exposure as well as the interaction between them across ancestry. Methods: Data were drawn from the Spit for Science (S4S) study, a US college student population, where participants reported on IPT exposure prior to college and alcohol consumption and problems during college (N = 9,006; ancestry: 21.3% African [AFR], 12.5% Admixed Americas [AMR], 9.6% East Asian [EAS], 48.1% European [EUR], 8.6% South Asian [SAS]). Two trans-ancestry PGS were constructed, one for alcohol consumption and another for AUD, using large-scale GWAS summary statistics from multiple ancestries weighted using PRS-CSx. Regression models were applied to test for the presence of associations between alcohol-PGS and IPT main and interaction effects. Results: In the meta-analysis across ancestry groups, IPT exposure and PGS were significantly associated with alcohol consumption (ßIPT = 0.31, P IPT = 0.0002; ßPGS = 0.09, P PGS = 0.004) and AUD (ORIPT = 1.12, P IPT = 3.5 × 10-8; ORPGS = 1.02, P PGS = 0.002). No statistically significant interactions were detected between IPT and sex nor between IPT and PGS. When inspecting ancestry specific results, the alcohol consumption-PGS and AUD-PGS were only statistically significant in the EUR ancestry group (ßPGS = 0.09, P PGS = 0.04; ORPGS = 1.02, P PGS = 0.022, respectively). Discussion: IPT exposure prior to college was strongly associated with alcohol outcomes in this college-age sample, which could be used as a preventative measure to identify students at high risk for problematic alcohol use. Additionally, results add to developing evidence of polygenic score association in meta-analyzed samples, highlighting the importance of continued efforts to increase ancestral representation in genetic studies and inclusive analytic approaches to increase the generalizability of results from genetic association studies.

A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations.

Abstinence rates among smokers attempting to quit remain low despite the wide availability and accessibility of pharmacological smoking cessation treatments. In addition, the prevalence of cessation attempts and abstinence differs by individual-level social factors such as race and ethnicity. Clinical treatment of nicotine dependence also continues to be challenged by individual-level variability in effectiveness to promote abstinence. The use of tailored smoking cessation strategies that incorporate information on individual-level social and genetic factors hold promise, although additional pharmacogenomic knowledge is still needed. In particular, genetic variants associated with pharmacological responses to smoking cessation treatment have generally been conducted in populations with participants that self-identify as White race or who are determined to be of European genetic ancestry. These results may not adequately capture the variability across all smokers as a result of understudied differences in allele frequencies across genetic ancestry populations. This suggests that much of the current pharmacogenetic study results for smoking cessation may not apply to all populations. Therefore, clinical application of pharmacogenetic results may exacerbate health inequities by racial and ethnic groups. This scoping review examines the extent to which racial, ethnic, and ancestral groups that experience differences in smoking rates and smoking cessation are represented in the existing body of published pharmacogenetic studies of smoking cessation. We will summarize results by race, ethnicity, and ancestry across pharmacological treatments and study designs. We will also explore current opportunities and challenges in conducting pharmacogenomic research on smoking cessation that encourages greater participant diversity, including practical barriers to clinical utilization of pharmacological smoking cessation treatment and clinical implementation of pharmacogenetic knowledge.

Genetic and environmental influences of white and gray matter signal contrast: a new phenotype for imaging genetics?

The estimation of cortical thickness is in part dependent on the degree of contrast in T1 signal intensity between white matter and gray matter along the cortical mantle. The ratio of white matter to gray matter signal (WM/GM contrast) has been found to vary as a function of age and Alzheimer's disease status, suggesting a biological component to what might otherwise be labeled as a nuisance variable. The aim of the present study was to determine if measures of WM/GM contrast are genetically influenced, as well as the degree to which this phenotype may be related to the genetic and environment determinants of cortical thickness. Participants were 514 male twins (130 monozygotic, 97 dizygotic pairs, and 60 unpaired individuals) from the Vietnam Era Twin Study of Aging. Ages ranged from 51 to 59 years. Measures of WM/GM contrast and cortical thickness were derived for 66 cortical regions of interest (ROI) using FreeSurfer-based methods. Univariate and bivariate twin analyses were used in order to estimate the heritability of WM/GM contrast, as well as the degree of shared genetic and environmental variance between WM/GM contrast and cortical thickness. WM/GM contrast was found to be significantly heritable in the majority of ROIs. The average heritability across individual ROIs was highest in the occipital lobe (.50), and lowest in the cingulate cortex (.24). Significant phenotypic correlations between WM/GM contrast and cortical thickness were observed for most of the ROIs. The majority of the phenotypic correlations were negative, ranging from ?.11 to ?.54. Of the 66 associations, only 17 significant genetic correlations were found, ranging from ?.16 to ?.34, indicating small amounts of shared genetic variance. The majority of the phenotypic correlations were accounted for by small unique environmental effects common between WM/GM contrast and cortical thickness. These findings demonstrate that like cortical thickness, WM/GM contrast is a genetically influenced brain structure phenotype. The lack of significant genetic correlations with cortical thickness suggests that this measure potentially represents a unique source of genetic variance, one that has yet to be explored by the field of imaging genetics.

White matter heritability using diffusion tensor imaging in neonatal brains.

Understanding genetic and environmental effects on white matter development in the first years of life is of great interest, as it provides insights into the etiology of neurodevelopmental disorders. In this study, the genetic and environmental effects on white matter were estimated using data from 173 neonatal twin subjects. Diffusion tensor imaging scans were acquired around 40 days after birth and were non-rigidly registered to a group-specific atlas and parcellated into 98 ROIs. A model of additive genetic, and common and specific environmental variance components was used to estimate overall and regional genetic and environmental contributions to diffusion parameters of fractional anisotropy, radial diffusivity, and axial diffusivity. Correlations between the regional heritability values and diffusion parameters were also examined. Results indicate that individual differences in overall white matter microstructure, represented by the average diffusion parameters over the whole brain, are heritable, and estimates are higher than found in studies in adults. Estimates of genetic and environmental variance components vary considerably across different white matter regions. Significant positive correlations between radial diffusivity heritability and radial diffusivity values are consistent with regional genetic variation being modulated by maturation status in the neonatal brain: the more mature the region is, the less genetic variation it shows. Common environmental effects are present in a few regions that tend to be characterized by low radial diffusivity. Results from the joint diffusion parameter analysis suggest that multivariate modeling approaches might be promising to better estimate maturation status and its relationship with genetic and environmental effects.

A network approach to substance use, internalizing, and externalizing comorbidity in U.S. adults.

INTRODUCTION: Use of conventional cigarettes (CIG), alcohol, marijuana, and sedatives [i.e., benzodiazepines and barbiturates]) commonly co-occur with internalizing and externalizing disorders. It is unclear how these relationships extend to electronic cigarettes (ECIGs) and prescription drugs not prescribed (i.e., sedatives, tranquilizers, and painkillers [PDNP]), and whether they differ by gender. METHODS: Adult data (N = 30,211) from Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study were used to estimate a network of current or past-month use for six substances, experiencing four internalizing symptoms in the past month, and experiencing seven externalizing symptoms in the past month. Visual comparisons, global strength invariance, network structure invariance, and edge strength invariance were tested to detail substance use and internalizing/externalizing symptom networks. RESULTS: Overall, networks were consistent between men and women. The strongest substance use/mental health symptom connections estimated as edge-weights (EW) were between marijuana with lying (EW = 0.60, 95% CI = 0.49; 0.70), marijuana with engaging in fights (EW = 0.54, 95% CI = 0.27; 0.81), PDNP with having trouble sleeping (EW = 0.53, 95% CI = 0.40; 0.66), and alcohol and impulsivity (EW = 0.48, 95% CI = 0.42; 0.53). DISCUSSION: There were many weak connections throughout the substance use and internalizing/externalizing network. A few important connections were identified and encourage future study. In particular, PDNP was most strongly associated with internalizing symptoms. Marijuana, alcohol and PDNP use were most strongly associated with externalizing symptoms.

Polygenic score for cigarette smoking is associated with ever electronic-cigarette use in a college-aged sample.

BACKGROUND AND AIMS: Electronic cigarette use has escalated rapidly in recent years, particularly among youth. Little is known about the genetic influences on e-cigarette use. This study aimed to determine whether genetic risk for regular use of combustible cigarettes or for number of cigarettes smoked per day confers risk for ever e-cigarette use or frequency of e-cigarette use. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We used data from 9541 young adults from the Spit for Science longitudinal cohort study (2011-2019). Polygenic scores (PGS) of regular combustible cigarette use (PGS-RCU) and cigarettes per day (PGS-CPD) were constructed using summary statistics from the two largest available genome-wide association study (GWAS) meta-analysis of European ancestry and East Asian ancestry of combustible cigarette use and used to test whether the PGS of RCU or CPD predicted lifetime e-cigarette use and frequency of past 30-day e-cigarette use in a diverse sample of young adults of African (AFR), Admixed American (AMR), East Asian (EAS), European (EUR), and South Asian (SAS) ancestry. FINDINGS: The PGS-RCU was associated with lifetime e-cigarette use in the EUR sample (OR = 1.27, 95% CI = 1.19-1.36, P = 7.53 × 10-12 ), but not in the other subsamples (ps > 0.12). This association remained significant after excluding regular combustible cigarette smokers (OR = 1.21, 95% CI = 1.12-1.31, P = 3.36 × 10-6 ). There was no statistically significant association between PGS-CPD and lifetime e-cigarette use and neither the PGS-RCU nor the PGS-CPD were associated with frequency of e-cigarette use in the past 30 days in any of the subsamples. CONCLUSIONS: Genetic factors associated with regular combustible cigarette use appear to be associated with ever e-cigarette use in young adults. We did not find evidence for shared genetic factors influencing heaviness of use of combustible cigarettes and current e-cigarette use frequency.

The association between internalizing and externalizing severity with current use of cigarettes, e-cigarettes, and alcohol in adults: Wave 1 of the Population Assessment of Tobacco and Health (PATH) study.

INTRODUCTION: Concurrent tobacco/alcohol use is common in adults, and associated with the severity of symptoms experienced by those with mental health disorders. However, few studies have explored this relationship across different combinations of tobacco products [i.e., conventional cigarette (CC) and electronic cigarette (EC)] and alcohol. METHODS: Data from the Wave 1 (2013-2014) Population Assessment of Tobacco and Health study were used. A total of 15,947 adults aged 18 years or older with complete study information were included. Multinomial logistic regression analyses were performed to determine the relationship between lifetime internalizing/externalizing severity and past 30-day use of tobacco and alcohol, adjusting for nicotine dependence (ND), sex, age, race, education, and income. RESULTS: Internalizing severity was more strongly associated with CC and alcohol use (moderate AOR = 1.47, 95% CI = 1.22-1.77; high AOR = 1.29, 95% CI = 1.03-1.61) as well as alcohol-exclusive use (moderate AOR = 1.58, 95% CI = 1.27-1.96; high AOR = 1.31, 95% CI = 1.05-1.64) while externalizing severity was more strongly associated with EC and alcohol use (high AOR = 2.97, 95% CI = 1.84-4.81, moderate AOR = 2.29, 95% CI = 1.53-3.43) when accounting for ND compared to none. The relationship between externalizing severity with EC use was dependent on alcohol being used with EC. CONCLUSIONS: The associations between psychopathology (internalizing vs. externalizing severity) varies by different combinations of alcohol, CC, and EC. Further, these relationships may be mediated through ND. Future investigations into the comorbidity between mental disorder symptoms with tobacco and alcohol use should consider use of specific substances as well as their combination.

Developing community-based health education strategies with family history: Assessing the association between community resident family history and interest in health education.

BACKGROUND: Family history (FH) is an underutilized genetically informative tool that can influence disease prevention and treatment. It is unclear how FH fits into the development of community-based health education. This study examines the role that FH plays in perceived threat and health education related to mental and chronic physical conditions in the context of the health belief model. METHODS: Data were collected from 1,048 adult participants aged 18-90 years. Approximately 76% of participants indicated African-American race/ethnicity and 35% had less than high school level education. Self-report data were collected on FH of four disorders: anxiety, depression, diabetes, and high blood pressure. Interest in receiving information regarding prevention as well as future testing efforts was assessed broadly. A series of logistic regressions examined the association between FH for each of the disorders and interest in receiving information on (1) prevention of diseases in general and (2) testing for diseases in general. These associations were also analyzed after accounting for the influence of perceived threat of conditions. RESULTS: Interest in receiving general health education was significantly associated with FH of depression (OR = 2.72, 95% CI = 1.74-4.25), anxiety (OR = 2.26, 95% CI = 1.45-3.22), and high blood pressure (OR = 2.54, 95% CI = 1.05-6.12). After adjustment for perceived threat, the magnitude of these associations was reduced substantially. The associations between perceived threat and either interest in receiving information on disease testing or receiving general health education were strong and significant across all conditions (OR = 2.11-3.74). DISCUSSION: These results provide evidence that perceived threat mediates the association between FH and engagement with health education. Currently available health education programs may benefit from considering the role of FH in an individual's motivation for participation in health education activities alongside other factors.