Asthma and chronic obstructive pulmonary disease are characterized by chronic airway inflammation. Studies using bronchoalveolar lavage (BAL) have shown an increased proportion of eosinophils in the BAL fluid from asthmatics compared with that from normal subjects, whereas studies of chronic obstructive pulmonary disease (COPD) have shown increased numbers of neutrophils. Induced sputum allows sampling of respiratory tract secretions from patients and control subjects, providing a noninvasive method of studying airway secretions and allowing characterization of cells and measurement of soluble markers. We investigated whether induced sputum was a useful method of studying airway fluid from patients with moderate to severe COPD and whether it could be used to compare inflammation in this condition with that in asthma. An initial reproducibility study was undertaken. Sputum was induced twice in 13 patients with severe COPD at a 14-d interval. Total and differential cell counts were carried out and were found to be reproducible over this period. Sputum was then induced in 14 patients with COPD, 23 patients with asthma, 12 healthy cigarette smokers, and 16 normal nonsmoking control subjects. We found a significant increase in neutrophils and increased concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) in the patients with COPD compared with the smoking and nonsmoking control subjects. Interleukin-8, but not TNF alpha, was significantly higher in the COPD group than in the asthmatic group. We conclude that the cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.

ehaviors related to self-regulation, such as substance use disorders or antisocial behaviors, have far-reaching consequences for affected individuals, their families, communities and society at large 1,2 . Collectively, this group of correlated traits are classified as externalizing 3 . Twin studies have demonstrated that externalizing liability is highly heritable (~80%) 4,5 . To date, however, no large-scale molecular genetic studies have utilized the extensive degree of genetic overlap among externalizing traits to aid gene discovery, as most studies have focused on individual disorders 6 . For many high-cost, high-risk behaviors with an externalizing component-opioid use disorder and suicide attempts 7 being salient examples-there are limited genotyped cases available for gene discovery 8,9 .A complementary strategy to the single-disease approach is to study the shared genetic architecture across traits in multivariate analyses, which boosts statistical power by pooling data across

Genome‐wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (eg, ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWAS of DSM‐IV AD (primary analysis), DSM‐IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7418 (1121 families) European American (EA) individuals from the Collaborative Study on the Genetics of Alcoholism (COGA). Trans‐ancestral meta‐analyses combined these results with data from 3175 (585 families) African‐American (AA) individuals from COGA. In the EA GWAS, three loci were genome‐wide significant: rs1229984 in ADH1B for AD criterion count (P = 4.16E−11) and Desire to cut drinking (P = 1.21E−11); rs188227250 (chromosome 8, Drinking more than intended, P = 6.72E−09); rs1912461 (chromosome 15, Time spent drinking, P = 1.77E−08). In the trans‐ancestral meta‐analysis, rs1229984 was associated with multiple phenotypes and two additional loci were genome‐wide significant: rs61826952 (chromosome 1, DSM‐IV AD, P = 8.42E−11); rs7597960 (chromosome 2, Time spent drinking, P = 1.22E−08). Associations with rs1229984 and rs18822750 were replicated in independent datasets. Polygenic risk scores derived from the EA GWAS of AD predicted AD in two EA datasets (P < .01; 0.61%‐1.82% of variance). Identified novel variants (ie, rs1912461, rs61826952) were associated with differential central evoked theta power (loss − gain; P = .0037) and reward‐related ventral striatum reactivity (P = .008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability.

ABSTRACT. Objective: Racial discrimination has been identifi ed as an important predictor of alcohol-related outcomes for African Americans. The goal of the current study was to extend previously found links between lifetime discrimination, alcohol use, and alcohol problems as well as to elucidate the affective mechanisms underlying these associations, as moderated by gender. Method: A multiple-groups structural equation model was computed using survey data collected from 619 students from a historically Black college/university. Results: The fi nal model provided excellent fi t to the data, explaining 6% of the variance in alcohol consumption and 37% of the variance in alcohol problems. Discrimination was a signifi cant predictor of alcohol-related problems but not, by and large, level of use. For men, anger-but not discriminationspecifi c anger-was a signifi cant partial mediator of the link between discrimination and both alcohol use and alcohol problems. Depression partially mediated the link between discrimination and alcohol problems for both men and women. Conclusions: The results suggest that, for African Americans whose drinking leads to drinking-related problems, discrimination and poor affective self-regulation are highly relevant and predictive factors, especially for men. (J. Stud. Alcohol Drugs, 75, 228-234, 2014)

Background and Objectives There have been remarkable advances in understanding genetic influences on complex traits; however, individuals of African descent have been underrepresented in genetic research. Methods We review the limitations of existing genetic research on alcohol phenotypes in African Americans (AA) including both twin and gene identification studies, possible reasons for underrepresentation of AAs in genetic research, the implications of the lack of racially diverse samples, and special considerations regarding conducting genetic research in AA populations. Results There is a marked absence of large-scale AA twin studies so little is known about the genetic epidemiology of alcohol use and problems among AAs. Individuals of African descent have also been underrepresented in gene identification efforts; however, there have been recent efforts to enhance representation. It remains unknown the extent to which genetic variants associated with alcohol use outcomes in individuals of European and African descent will be shared. Efforts to increase representation must be accompanied by careful attention to the ethical, legal, and social implications of genetic research. This is particularly true for AAs due to the history of abuse by the biomedical community and the persistent racial discrimination targeting this population. Conclusions and Scientific Significance Lack of representation in genetic studies limits our understanding of the etiological factors that contribute to substance use and psychiatric outcomes in populations of African descent and has the potential to further perpetuate health disparities. Involving individuals of diverse ancestry in discussions about genetic research will be critical to ensure that all populations benefit equally from genetic advances.

Despite evidence that African Americans are disproportionately affected by drinking to cope relative to European Americans, African-American college students’ drinking motives remain understudied. Additionally, most research has only examined between-person differences in drinking to cope as a predictor of alcohol use, ignoring within-person variability. In the current daily diary study of 462 African-American undergraduates from a historically Black university, associations between episode-specific drinking to cope and alcohol use were tested, an approach more consistent with motivational theories of drinking. At baseline, students completed traditional global drinking motive measures; then for 30 days they reported the number of standard drinks they consumed the previous night, and, if they drank, their coping, enhancement, and social reasons for doing so. Students who reported higher mean levels of episode-specific coping motives, on average, consumed more alcohol on drinking evenings. Furthermore, mean episode-specific coping motives, but not global coping motives, predicted average levels of alcohol use. Additionally, coping motives were particularly important for predicting nonsocial (versus social) drinking. Finally, during evenings for which students reported higher than usual episode-specific coping motives, men consumed more alcohol in both social and nonsocial contexts; in contrast, women reporting higher than usual drinking-to-cope motives only consumed more nonsocial drinks. In conclusion, drinking among African-American college students was related to coping motives, particularly among men and in the context of nonsocial alcohol consumption. Moreover, motivational theories of alcohol use may be refined by measuring episode-specific drinking motives that more accurately capture the drinking-to-cope process.

Background Covault et al. (2007) reported that the common functional polymorphism, 5-HTTLPR, in the serotonin transporter gene moderated the association between past-year stressful events and daily reports of drinking in a sample of European-American (EA) college students. We examined this effect in college students of African descent. Methods Students recruited at a Historically Black University (n=564) completed web-based measures of past-year stressful life experiences and daily reports of drinking and heavy drinking over a 30-day period. Participants were genotyped for the tri-allelic 5-HTTLPR polymorphism and dichotomized as low-activity S’ allele carriers or high-activity L’ homozygotes. Generalized linear models were used to examine the effects of life stress, genotype, and their interaction on the two drinking measures. Results In students who completed 15 or more daily surveys (n=393), there was a significant interaction of past-year stressful events, 5-HTTLPR genotype, and gender on the number of drinking days (p=0.002). Similar findings were obtained in relation to heavy drinking days (p=0.007). Men showed a main effect of past-year stressful events on both drinking outcomes (p’s<0.001), but no main or moderator effects of genotype. In women, the S’ allele moderated the impact of past-year life stressors on the frequency of drinking and heavy drinking days (p’s<0.001). Conclusions In college students of African descent, past-year stressful events were associated with more frequent drinking and heavy drinking, an effect that was moderated by the 5-HTTLPR polymorphism. However, in contrast to the findings in EA students, in the current sample, 5-HTTLPR moderated the association only among women.

Fast beta (20–28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10−8. The most significantly associated SNP, rs11720469 (β: − 0.124; P<4.5 × 10−9), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.