Investigating Associations of Substance Use and Dependence With Planned Versus Unplanned Suicide Attempt.

OBJECTIVE: The present analyses investigated substance use and dependence as correlates of past-year suicide attempt and of unplanned versus planned suicide attempt in a nationally representative sample. METHOD: Participants were 214,505 adults (52% female; 64% White, 12% Black, <1% Native American, <1% Pacific Islander, 6% Asian, 16% Hispanic, 2% multiracial) from the 2015-2019 National Surveys on Drug Use and Health. Four logistic regression models were constructed. Models 1 and 2 examined substance use and dependence, respectively, as correlates of suicide attempt. Models 3 and 4 evaluated whether substance use and dependence were related to suicide attempt in the absence of a plan. RESULTS: In Models 1 and 2, higher cigarette smoking and marijuana use; any use of opioids, sedatives, and hallucinogens; and greater dependence on nicotine, alcohol, marijuana, and any illicit or prescription drug were associated with elevated risk for suicide attempt. Associations with cigarette smoking, sedative use, and dependence on nicotine, alcohol, and any illicit or prescription drug remained statistically significant in sensitivity analyses limited to individuals with suicidal ideation. In Models 3 and 4, substance use and dependence were unrelated to risk for unplanned (vs. planned) suicide attempt. CONCLUSIONS: Although substance-related outcomes are consistently associated with suicide attempt, there was little evidence that substance use and dependence are related to risk for unplanned versus planned suicidal behavior.

Clinical, environmental, and genetic risk factors for substance use disorders: characterizing combined effects across multiple cohorts.

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

Principal Component Analysis Reduces Collider Bias in Polygenic Score Effect Size Estimation.

In this study, we test principal component analysis (PCA) of measured confounders as a method to reduce collider bias in polygenic association models. We present results from simulations and application of the method in the Collaborative Study of the Genetics of Alcoholism (COGA) sample with a polygenic score for alcohol problems, DSM-5 alcohol use disorder as the target phenotype, and two collider variables: tobacco use and educational attainment. Simulation results suggest that assumptions regarding the correlation structure and availability of measured confounders are complementary, such that meeting one assumption relaxes the other. Application of the method in COGA shows that PC covariates reduce collider bias when tobacco use is used as the collider variable. Application of this method may improve PRS effect size estimation in some cases by reducing the effect of collider bias, making efficient use of data resources that are available in many studies.

Patterns and Correlates of Polysubstance Use Among Individuals With Severe Alcohol Use Disorder.

AIM: The present study examined patterns and correlates of polysubstance use among individuals with severe alcohol use disorder (AUD). METHODS: Participants were 2785 individuals (63% female; mean age = 43 years, range = 18-78 years) from the Genes, Addiction and Personality Study. All participants met lifetime criteria for severe AUD (6+ symptoms). We used latent class analysis to identify patterns of frequency of lifetime use for cigarettes, marijuana, cocaine, stimulants, sedatives, opioids and hallucinogens. A variety of demographic and behavioral correlates of latent class membership were tested in univariable and multivariable models. RESULTS: A five-class solution was selected: extended range polysubstance use (24.5%); cigarette and marijuana use (18.8%); 'testers,' characterized by high probabilities of smoking 100 or more cigarettes, using marijuana 6+ times, and trying the remaining substances 1-5 times (12.3%); moderate range polysubstance use (17.1%) and minimal use (reference class; 27.3%). In univariable analyses, all potential correlates were related to latent class membership. In the multivariable model, associations with gender, race/ethnicity, age of onset for alcohol problems, dimensions of impulsivity, depressive symptoms, antisocial behavior and family history density of alcohol problems remained significant, though the pattern and strength of associations differed across classes. For instance, sensation-seeking, lack of premeditation and family history were uniquely associated with membership in the extended range polysubstance use class. CONCLUSION: Patterns of polysubstance use are differentially related to demographic and behavioral factors among individuals with severe AUD. Assessing use across multiple substances may inform the selection of targets for treatment and prevention.

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

BACKGROUND AND AIMS: The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis). DESIGN: Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families. SETTING: Six sites in the United States. PARTICIPANTS: European ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample. MEASUREMENTS: Outcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment. FINDINGS: In polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R2 ) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R2 0.13-0.20%). CONCLUSIONS: Individuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education).

Which adolescent factors predict alcohol misuse in young adulthood? A co-twin comparisons study.

BACKGROUND AND AIMS: Research on adolescent predictors of later alcohol misuse is typically conducted on samples of singletons, and associations may be confounded by between-family differences. To address potential confounding, we applied a co-twin comparison design to evaluate whether differences between co-twins in a wide array of adolescent risk factors predicted differences in young adult alcohol misuse. DESIGN: Longitudinal study in which associations between characteristics of the sample as adolescents were used to predict young adult alcohol misuse in individual-level analyses and co-twin comparisons. SETTING: Finland. PARTICIPANTS: A total of 3402 individuals (1435 complete twin pairs; 36% monozygotic; 57% female) from the FinnTwin12 study. MEASUREMENTS: The young adult alcohol misuse outcome was a composite score of alcohol use and intoxication frequency. Adolescent predictors included factor scores representing academic performance, substance use, externalizing problems, internalizing problems, peer environment, physical health and relationship with parents; and single measures tapping alcohol expectancies, life events and pubertal development. FINDINGS: In individual-level analyses, individuals with higher adolescent substance use, externalizing problems, time with friends, peer deviance, sports involvement, sleeping difficulties, parental discipline, positive alcohol expectancies and difficulty of life events reported higher alcohol misuse in young adulthood (Ps < 0.019, R2  = 0.0003-0.0310%). Conversely, those with higher adolescent internalizing problems, parent-child relationship quality and time with parents reported lower alcohol misuse (Ps < 0021, R2  = 0.0018-0.0093%). The associations with adolescent substance use and alcohol expectancies remained significant in co-twin comparisons (Ps < 0.049, R2  = 0.0019-0.0314%). Further, academic performance emerged as a significant predictor, such that individuals with higher grades compared with their co-twin reported higher young adult alcohol misuse (Ps < 0.029, R2  = 0.0449-0.0533%). CONCLUSIONS: Adolescent substance use, positive alcohol expectancies and higher academic performance appear to be robust predictors of later alcohol misuse.