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Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene-environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent externalizing behavior across two time-points in a high-risk longitudinal sample of 1,200 adolescents (764 European and 436 African ancestry; M(age) = 12.99) from the Collaborative Study on the Genetics of Alcoholism. Results from multivariate path analysis indicated that externalizing polygenic scores were directly associated with adolescent externalizing behavior but also indirectly via peer substance use, in the European ancestry sample. No significant polygenic association nor indirect effects of genetic risk were observed in the African ancestry group, likely due to more limited power. Our findings underscore the importance of gene-environment interplay and suggest peer substance use may be a mechanism through which genetic risk influences adolescent externalizing behavior.

College students demonstrate high rates of depression and anxiety, particularly among students with self-reported history of trauma exposure. Neuroticism, a personality trait characterized by emotional instability and negative affect, is consistently associated with internalizing symptoms; however, our understanding of malleable risk characteristics that help to clarify these associations between neuroticism and internalizing symptoms is limited. The current study investigated whether anxiety sensitivity (AS) and/or distress tolerance (DT) would predict changes in internalizing symptoms (depression and anxiety), beyond the effects of neuroticism, in a high-risk sample of college students. Participants were 316 college students (75.9% women) with self-reported history of interpersonal trauma exposure who participated in a university-wide longitudinal study of emotional health. Participants completed assessments of personality, AS, DT, depression, and anxiety over three time points spanning an average of 26 months. Results of structural equation modeling demonstrated that higher AS predicted increases in depression and anxiety, and lower DT predicted increases in depression and anxiety (controlling for neuroticism). Neuroticism did not predict changes in depression or anxiety. These findings contribute to our understanding of the role of AS and DT in the development of depression and anxiety in trauma-exposed college students.

OBJECTIVE. Analyzed relationships among social and environmental determinants serving as risk, protective, and important covariate factors for mental health risk and help-seeking among Black men on a college campus. METHODS. A secondary data analysis was conducted utilizing an ongoing, campus-wide survey at a large, urban, public university. Measures included depressive and anxiety symptoms; campus service utilization; risk factors (e.g. financial status); protective factors (social support/religiosity); and additional covariates (substance use/GPA). Multiple linear regressions were conducted to examine relationships between these factors, symptoms and help-seeking. RESULTS. Data is included for 681 students. Findings indicated that stressful life events were associated with higher levels of anxiety symptoms (B = 0.39, p < 0.001) and depressive symptoms (B = 0.33, p = 0.013). Cannabis use (B = 1.14, p= .020) was also associated with higher levels of depressive symptoms. We found that financial status (B = 0.21, p = 0.041) was positively associated with higher levels of depressive symptoms and endorsement of religiosity was associated with lower levels anxiety (B = −0.23, p = 0.019) and depressive symptoms (B = −0.32, p = 0.035). Religiosity predicted lower utilization of campus health services. CONCLUSIONS. The key findings indicated that Black men’s mental health is negatively influenced by stressful live events and cannabis use. As religiosity was associated with lower levels of symptoms and utilization, it may be beneficial to assess this in future work. Further research is needed to address and improve mental health and help-seeking among these men.

Exposure to trauma (particularly interpersonal trauma), post-traumatic stress disorder (PTSD) symptoms, and low distress tolerance (DT; the ability to tolerate negative internal states), are all related to risk for alcohol use disorders (AUD). The aim of this study was to examine the main and interactive effects of PTSD symptom severity and DT in relation to current (past 30-day) alcohol consumption and binge drinking among emerging adult men and women with a history of sexual/physical assault. Participants were 572 undergraduate students (66% women) with a history of physical/sexual assault endorsing past month alcohol use. Participants completed the Distress Tolerance Scale (DTS), the PTSD Checklist for DSM-V (PCL-5), and an abbreviated Timeline Followback Questionnaire (TLFB), which assessed past 30-day total alcohol consumption (i.e., total number of drinks) and binge drinking frequency (i.e., 5+ drinks [4+ for women]). Negative binomial regression analyses revealed that male sex, higher trauma load (i.e., total number of trauma categories endorsed), and higher PTSD symptom severity were associated with both higher number of total drinks and higher frequency of binge drinking episodes. However, DT was not associated with either alcohol outcome when PTSD symptom severity was entered in the models. The interaction of PTSD symptom severity and DT was not significantly associated with total alcohol consumption or binge drinking. These results highlight the importance of investigating the unique contributions of PTSD symptoms and DT (as well as other transdiagnostic cognitive-affective constructs) in the onset and maintenance of AUD.

Aberrant connectivity of large-scale brain networks has been observed among individuals with alcohol use disorders (AUDs) as well as in those at risk, suggesting deficits in neural communication between brain regions in the liability to develop AUD. Electroencephalographical (EEG) coherence, which measures the degree of synchrony between brain regions, may be a useful measure of connectivity patterns in neural networks for studying the genetics of AUD. In 8810 individuals (6644 of European and 2166 of African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Multi-Trait Analyses of genome-wide association studies (MTAG) on parietal resting-state theta (3–7 Hz) EEG coherence, which previously have been associated with AUD. We also examined developmental effects of GWAS findings on trajectories of neural connectivity in a longitudinal subsample of 2316 adolescent/young adult offspring from COGA families (ages 12–30) and examined the functional and clinical significance of GWAS variants. Six correlated single nucleotide polymorphisms located in a brain-expressed lincRNA (ENSG00000266213) on chromosome 18q23 were associated with posterior interhemispheric low theta EEG coherence (3–5 Hz). These same variants were also associated with alcohol use behavior and posterior corpus callosum volume, both in a subset of COGA and in the UK Biobank. Analyses in the subsample of COGA offspring indicated that the association of rs12954372 with low theta EEG coherence occurred only in females, most prominently between ages 25 and 30 (p

Shared genetic factors contribute to the high degree of comorbidity among externalizing problems (e.g. substance use and antisocial behavior). We leverage this common genetic etiology to identify genetic influences externalizing problems in participants from the Collaborative Study on the Genetics of Alcoholism (European ancestry = 7,568; African ancestry = 3,274). We performed a family-based genome-wide association study (GWAS) on externalizing scores derived from criterion counts of five DSM disorders (alcohol dependence, alcohol abuse, illicit drug dependence, illicit drug abuse, and either antisocial personality disorder or conduct disorder). We meta analyzed these results with a similar measure of externalizing in an independent sample, Spit for Science (combined sample N = 15,112). We did not discover any robust genome-wide significant signals. Polygenic scores derived from the ancestry-specific GWAS summary statistics predicted externalizing problems in an independent European ancestry sample, but not in those of African ancestry. However, these PRS were no longer significant after adjusting for multiple testing. Larger samples with deep phenotyping are necessary for the discovery of SNPs related to externalizing problems.

Genetic effects on alcohol use can vary over time but are often examined using longitudinal models that predict a distal outcome at a single time point. The vast majority of these studies predominately examine effects using White, European American (EA) samples or examine the etiology of genetic variants identified from EA samples in other racial/ethnic populations, leading to inconclusive findings about genetic effects on alcohol use. The current study examined how genetic influences on alcohol use varied by age across a 15 year period within a diverse ethnic/racial sample of adolescents. Using a multi-ethnic approach, polygenic risk scores were created for African American (AA, n = 192) and EA samples (n = 271) based on racially/ethnically aligned genome wide association studies. Age-varying associations between polygenic scores and alcohol use were examined from age 16 to 30 using time-varying effect models separately for AA and EA samples. Polygenic risk for alcohol use was found to be associated with alcohol use from age 22–27 in the AA sample and from age 24.50 to 29 in the EA sample. Results are discussed relative to the intersection of alcohol use and developmental genetic effects in diverse populations.

Previous research suggests that genetic risk factors may predispose to conduct problems and alcohol use in adolescence. Whether genetic risk factors interact with social contexts has not been well characterized among African American adolescents. Data came from a subsample of the Genes, Environment, and Neighborhood Initiative study comprising 501 African American adolescents, including 151 lifetime drinkers (56% female, mean age = 16.3, SD = 1.4). Genetic risk was assessed with polygenic risk scores for alcohol dependence. Analyses explored interactions between genetic risk and self-reported alcohol use, conduct problems, life stressors, and other covariates. The effects of two gene-environment interactions (G × E) were tested in the sample of alcohol exposed adolescents; one on conduct problems and the other on alcohol use. There were significant associations between polygenic risk for alcohol dependence and conduct problems. A significant G × E interaction showed the impact of genetic risk on conduct problems was stronger under conditions of high exposure to family and neighborhood stressors. Among this sample of African American adolescents, genetic risk for alcohol dependence was not directly associated with alcohol use but was related to more conduct problems. Further, the effect of genetic risk interacted with stressors from the family and neighborhood, so that the effect of genetic risk on conduct problems was stronger for individuals who reported greater stressors.

This study investigated internalizing problems, externalizing problems, and polydrug use among African-American youth residing in high-poverty neighborhoods, and tested the potential protective effects of religiosity, parental monitoring, and neighborhood collective efficacy on life stress and behavioral health outcomes (N = 576; 307 females; Mage = 16 years, SD = 1.44 years). A cumulative risk index reflected the combined effects of past year exposure to stressful life events, racial discrimination, and exposure to violence along with poor neighborhood ecology. Structural equation modeling revealed that cumulative risk significantly predicted internalizing problems, externalizing problems, and polydrug use. Interaction tests showed that the association of cumulative risk with internalizing problems was buffered by adolescent religiosity and neighborhood collective efficacy. The association of cumulative risk with externalizing problems was buffered by parental monitoring and collective efficacy. Adolescent sex further moderated these effects. The findings of the present study collectively highlight potential for protective factors to buffer effects of cumulative risk on behavioral health outcomes among youth residing in high-risk neighborhoods.

Understanding how ethanol actions on brain signal transduction and gene expression lead to excessive consumption and addiction could identify new treatments for alcohol dependence. We previously identified glycogen synthase kinase 3-beta (Gsk3b) as a member of a highly ethanol-responsive gene network in mouse medial prefrontal cortex (mPFC). Gsk3b has been implicated in dendritic function, synaptic plasticity and behavioral responses to other drugs of abuse. Here, we investigate Gsk3b in rodent models of ethanol consumption and as a risk factor for human alcohol dependence. Stereotactic viral vector gene delivery overexpression of Gsk3b in mouse mPFC increased 2-bottle choice ethanol consumption, which was blocked by lithium, a known GSK3B inhibitor. Further, Gsk3b overexpression increased anxiety-like behavior following abstinence from ethanol. Protein or mRNA expression studies following Gsk3b over-expression identified synaptojanin 2, brain-derived neurotrophic factor and the neuropeptide Y Y5 receptor as potential downstream factors altering ethanol behaviors. Rat operant studies showed that selective pharmacologic inhibition of GSK3B with TDZD-8 dose-dependently decreased motivation to self-administer ethanol and sucrose and selectively blocked ethanol relapse-like behavior. In set-based and gene-wise genetic association analysis, a GSK3b-centric gene expression network had significant genetic associations, at a gene and network level, with risk for alcohol dependence in humans. These mutually reinforcing cross-species findings implicate GSK3B in neurobiological mechanisms controlling ethanol consumption, and as both a potential risk factor and therapeutic target for alcohol dependence.

Twin studies indicate that latent genetic factors overlap across comorbid psychiatric disorders. In this study, we used a novel approach to elucidate shared genetic factors across psychiatric outcomes by clustering single nucleotide polymorphisms based on their genome-wide association patterns. We applied latent profile analysis (LPA) to p-values resulting from genome-wide association studies across three phenotypes: symptom counts of alcohol dependence (AD), antisocial personality disorder (ASP), and major depression (MD), using the European-American case-control genome-wide association study subsample of the collaborative study on the genetics of alcoholism (N = 1399). In the 3-class model, classes were characterized by overall low associations (85.6% of SNPs), relatively stronger association only with MD (6.8%), and stronger associations with AD and ASP but not with MD (7.6%), respectively. These results parallel the genetic factor structure identified in twin studies. The findings suggest that applying LPA to association results across multiple disorders may be a promising approach to identify the specific genetic etiologies underlying shared genetic variance.

Accumulative evidence from recent genotype × intervention studies suggests that individuals carrying susceptible genotypes benefit more from intervention and provides one avenue to identify subgroups that respond differentially to intervention. This study examined the moderation by glucocorticoid receptor (NR3C1) gene variants of intervention effects on the developmental trajectories of alcohol abuse through adolescence. Participants were randomized into Fast Track intervention and control groups self-reported past-year alcohol abuse annually from grade 7 through 2 years post-high school and provided genotype data at age 21 (69% males; European Americans [EAs] = 270, African-Americans [AAs] = 282). Latent growth curve models were fit to examine developmental trajectories of alcohol abuse. The interactions of 10 single nucleotide polymorphisms (SNPs) in NR3C1 with intervention were examined separately. Both EAs and AAs showed significant increases in past-year alcohol abuse with substantial inter-individual differences in rates of linear growth. AAs showed lower general levels and slower rates of linear growth than EAs. Adjusting for multiple tests, one NR3C1 SNP (rs12655166) significantly moderated intervention effects on the developmental trajectories of alcohol abuse among AAs. Intervention effects on the rates of linear growth were stronger among AAs carrying minor alleles than those not carrying minor alleles. The findings highlight the importance of taking a developmental perspective on adolescent alcohol use and have implications for future intervention design and evaluation by identifying subgroups that could disproportionally benefit from intervention.

The article "Genetics of Perceived Family Interaction From 12 to 17 Years of Age", written by Karri Silventoinen, Jinni Su, Lea Pulkkinen, Peter Barr, Richard J. Rose, Danielle M. Dick, Jaakko Kaprio, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 24 May 2019 without open access.

Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 × 10(-6)) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 × 10(-7)), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 × 10(-7)) and PLCL1 genes (p = 4.1 × 10(-6)) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p ≤ 10(-4)) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 × 10(-3), 3 × 10(-6)), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.

Data on the prevalence of mental health disorders for low-income, urban African American adolescents are scarce. This study presents data about the burden of mental disorders for this understudied population.Mental disorders were assessed using the Diagnostic Interview Schedule for Children (C-DISC), Youth Self-Report (YSR), and Child Behavior Checklist (CBCL) among a sample of adolescents and their caregivers from very impoverished neighborhoods in a Southern city.Based on the C-DISC, 3.8, 5.1 and 7.7% of adolescents met diagnostic criteria for major depression, post-traumatic stress disorder, and conduct disorder, respectively. There were significant differences among some of the mental health disorders based on adolescent and caregiver characteristics such as sex, school status, caregiver work status, and income level. We found a low prevalence of alcohol, marijuana, and substance abuse and dependence disorders.Information about the prevalence of mental health disorders in specific communities and populations can assist in addressing unmet needs, planning for services and treatment, and reducing health disparities.

Several studies have identified genes associated with alcohol use disorders, but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism (COGA) to identify novel genes affecting risk for alcohol dependence. To maximize the power of the extended family design we used a quantitative endophenotype, measured in all individuals: number of alcohol dependence symptoms endorsed (symptom count). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with symptom count were also associated with the dichotomous phenotype, DSM-IV alcohol dependence. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol (p=4.5×10−8, inflation corrected p=9.4×10−7). Results with DSM-IV alcohol dependence in the regions of interest support our findings with symptom count, though the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: non-overlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian twin-family study of alcohol use disorders (OZALC). Nominal association of C15orf53 with symptom count was observed in SAGE. The variant that showed strongest association with symptom count, rs12912251 and its highly correlated variants (D′=1, r2≥ 0.95), has previously been associated with risk for bipolar disorder.

Prevalence differences in depressive symptoms between the sexes typically emerge in adolescence, with symptoms more prevalent among girls. Some evidence suggests that variation in onset and progression of puberty might contribute to these differences. This study used a genetically informative, longitudinal (assessed at ages 12, 14, and 17) sample of Finnish adolescent twins (N = 1214, 51.6% female) to test whether etiological influences on depressive symptoms differ as a function of pubertal status. These tests were conducted separately by sex, and explored longitudinal relationships. Results indicated that pubertal development moderates environmental influences on depressive symptoms. These factors are more important on age 14 depressive symptoms among more developed girls relative to their less developed peers, but decrease in influence on age 17 depressive symptoms. The same effects are observed in boys, but are delayed, paralleling the delay in pubertal development in boys compared to girls. Thus, the importance of environmental influences on depressive symptoms during adolescence changes as a function of pubertal development, and the timing of this effect differs across the sexes.

Depressive symptoms and alcohol use are frequently positively associated during adolescence. This study aimed to assess the heritability of each phenotype across adolescence; to assess potential shared liabilities; to examine changes in the nature of shared liabilities across adolescence; and to investigate potential causal relationships between depressive symptoms and alcohol use. We studied a longitudinally assessed sample of adolescent Finnish twins (N = 1,282) to test hypotheses about genetic and environmental influences on these phenotypes within and across ages, using data from assessments at ages 12, 14, and 17.5 years. The heritability of depressive symptoms is consistent across adolescence (~40–50%), with contributions from common and unique environmental factors. The heritability of alcohol use varies across time (a2 = .25–.44), and age 14 alcohol use is heavily influenced by shared environmental factors. Genetic attenuation and innovation were observed across waves. Modest to moderate genetic (rA = .26–.59) and environmental (rC = .30–.63) correlations between phenotypes exist at all ages, but decrease over time. Tests for causal relationships between traits differed across ages and sexes. Intrapair MZ difference tests provided evidence for reciprocal causation in girls at ages 14 and 17.5. Formal causal models suggested significant causal relationships between the variables in both boys and girls. The association between depressive symptoms and alcohol use during adolescence is likely due to a combination of shared genetic and environmental influences and causal influences. These influences are also temporally dynamic, complicating efforts to understand factors contributing to the relationship between these outcomes. peerReviewed

We report genetic linkage and association findings which implicate the gene encoding the muscarinic acetylcholine receptor M2 (CHRM2) in the modulation of a scalp-recorded electrophysiological phenotype. The P3 (P300) response was evoked using a three-stimulus visual oddball paradigm and a phenotype that relates to the energy in the theta band (4-5 Hz) was analyzed. Studies have shown that similar electrophysiological measures represent cognitive correlates of attention, working memory, and response selection; a role has been suggested for the ascending cholinergic pathway in the same functions. The results of our genetic association tests, combined with knowledge regarding the presence of presynaptic cholinergic M2 autoreceptors in the basal forebrain, indicate that the cognitive processes required by the experiment may in part be mediated by inhibitory neural networks. These findings underscore the utility of electrophysiology and neurogenetics in the understanding of cognitive function and the study of brain-related disorders.

Results from twin studies suggest that overlapping genetic factors influence alcohol dependence and illicit drug dependence. Using data from the Collaborative Study on the Genetics of Alcoholism (COGA), we examined the association between 69 SNPs in the GABAA receptor gene cluster on chromosome 4 and marijuana and illicit drug dependence, individually, and as co-occurring phenotypes with alcohol dependence. Results suggested association between marijuana dependence and illicit drug dependence with SNPs in the GABRA2 gene. Interestingly, the evidence for association previously observed with alcohol dependence came only from individuals with comorbid illicit drug dependence. There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence.

We use findings from the behavior genetics literature about how genetic factors (latently) influence alcohol dependence and related disorders to develop and test hypotheses about the risk associated with a specific gene, GABRA2, across different developmental stages. This gene has previously been associated with adult alcohol dependence in the Collaborative Study of the Genetics of Alcoholism (COGA) sample [Edenberg, H. J., Dick, D. M., Xuei, X., Tian, H., Almasy, L., Bauer, L. O., Crowe, R., Goate, A., Hesselbrock, V., Jones, K. A., Kwon, J., Li, T. K., Nurnberger Jr., J. I., O'Connor, S. J., Reich, T., Rice, J., Schuckit, M., Porjesz, B., Foroud, T., and Begleiter, H. (2004). Am. J. Hum. Genet. 74:705-714] and other studies [Covault, J., Gelernter, J., Hesselbrock, V., Nellissery, M., and Kranzler, H. R. (2004). Am. J. Med. Genet. B Neuropsychiatr. Genet. 129B:104-109; Lappalainen, J., Krupitsky, E., Remizov, M., Pchelina, S., Taraskina, A., Zvartau, E., Somberg, L. K., Covault, J., Kranzler, H. R., Krystal, J., and Gelernter, J. (2005). Alcohol. Clin. Exp. Res. 29:493-498]. In a sample of children and adolescents ascertained as part of the COGA project, we find that GABRA2 is significantly associated with childhood conduct disorder symptoms, but not with childhood alcohol dependence symptoms. A consistent elevation in risk for alcohol dependence associated with GABRA2 is not evident until the mid-20s and then remains throughout adulthood. GABRA2 is also associated with other drug dependence in our sample, both in adolescence and adulthood.

Alcohol dependence is a common, complex disorder, which affects millions of people worldwide and causes considerable burden in terms of interpersonal and societal costs. Family, twin, and adoption studies have convincingly demonstrated that genes play an important role in the development of alcohol dependence, with heritability estimates in the range of 50% to 60% for both men and women. A number of studies are under way to identify specific genes involved in the predisposition toward alcohol dependence, and there is reason to be enthusiastic about recent progress. Several associated susceptibility genes are reviewed here, including genes involved in alcohol metabolism, as well as genes involved in GABAergic, endogenous opioid, dopaminergic, cholinergic, and serotonergic transmission. The next challenge will be to further characterize the risk associated with these susceptibility genes, examining how they may be related to comorbid disorders, developmental trajectories of risk, and potential moderation by environmental factors.

Intelligence, as measured by standardized psychological tests, has been shown to be highly heritable, though identifying specific genes influencing general intelligence has proven difficult. We conducted genome-wide linkage analyses to identify chromosomal regions containing genes influencing intelligence, as measured by WAIS full-scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ). Non-parametric multipoint linkage analyses were conducted with Merlin-regress software, using a sample of 1,111 genotyped and phenotyped individuals from 201 families, ascertained as part of the Collaborative Study on the Genetics of Alcoholism (COGA). The strongest evidence of linkage was obtained for FSIQ on chromosome 6 (LOD=3.28, 12 cM) near the marker D6S1006. This region was also implicated with suggestive linkage in a recently published genome screen of IQ in Australian and Dutch twin pairs, and it has been implicated in linkage studies of developmental dyslexia. Our findings provide further support that chromosome 6p contains gene(s) affecting intelligence.

Background A variety of species and experimental designs have been used to study genetic influences on alcohol dependence, ethanol response, and related traits. Integration of these heterogeneous data can be used to produce a ranked target gene list for additional investigation. Results In this study, we performed a unique multi-species evidence-based data integration using three microarray experiments in mice or humans that generated an initial alcohol dependence (AD) related genes list, human linkage and association results, and gene sets implicated in C. elegans and Drosophila. We then used permutation and false discovery rate (FDR) analyses on the genome-wide association studies (GWAS) dataset from the Collaborative Study on the Genetics of Alcoholism (COGA) to evaluate the ranking results and weighting matrices. We found one weighting score matrix could increase FDR based q-values for a list of 47 genes with a score greater than 2. Our follow up functional enrichment tests revealed these genes were primarily involved in brain responses to ethanol and neural adaptations occurring with alcoholism. Conclusions These results, along with our experimental validation of specific genes in mice, C. elegans and Drosophila, suggest that a cross-species evidence-based approach is useful to identify candidate genes contributing to alcoholism.