Assessing the Role of Long Noncoding RNA in Nucleus Accumbens in Subjects With Alcohol Dependence.

Background: Long noncoding RNA (lncRNA) have been implicated in the etiology of alcohol use. Since lncRNA provide another layer of complexity to the transcriptome, assessing their expression in the brain is the first critical step toward understanding lncRNA functions in alcohol use and addiction. Thus, we sought to profile lncRNA expression in the nucleus accumbens (NAc) in a large postmortem alcohol brain sample.

Impact of disaster exposure severity: Cascading effects across parental distress, adolescent PTSD symptoms, as well as parent-child conflict and communication.

Rationale: Natural disasters are common and have potentially deleterious impacts on individuals, as well as on the relationships among family members (Adams et al., 2015; Paul, 2015). Additionally, caregiver-, offspring-, and family-level outcomes are often correlated following disaster.

A preliminary investigation of rare variants associated with genetic risk for PTSD in a natural disaster-exposed adolescent sample.

: Posttraumatic stress disorder (PTSD) involves a complex interaction of biological, psychological, and social factors. Numerous studies have demonstrated genetic variation associated with the development of PTSD, primarily in adults. However, the contribution of low frequency and rare genetic variants to PTSD is unknown to date.

Lynch syndrome-associated ultra-hypermutated pediatric glioblastoma mimicking a constitutional mismatch repair deficiency syndrome.

Pediatric glioblastoma multiforme (GBM) has a poor prognosis as a result of recurrence after treatment of surgery and radiochemotherapy. A small subset of pediatric GBMs presenting with an ultra-high tumor mutational burden (TMB) may be sensitive to immune checkpoint inhibition. Here we report a 16-yr-old male with an ultra-hypermutated GBM.

Genetic and Environmental Predictors of Adolescent PTSD Symptom Trajectories Following a Natural Disaster.

Genes, environmental factors, and their interplay affect posttrauma symptoms. Although environmental predictors of the longitudinal course of posttraumatic stress disorder (PTSD) symptoms are documented, there remains a need to incorporate genetic risk into these models, especially in youth who are underrepresented in genetic studies. In an epidemiologic sample tornado-exposed adolescents ( = 707, 51% female, = 14.

Genetic and psychosocial predictors of alcohol use trajectories among disaster-exposed adolescents.

Background And Objectives: Adolescent alcohol misuse is associated with numerous long-term adverse outcomes, so we examined predictors of alcohol use among disaster-exposed adolescents, a group at-risk for alcohol misuse.

Methods: The current study (n = 332) examined severity of tornado-related exposure, posttraumatic stress disorder (PTSD) symptoms, emotional support, and a genetic risk sum score (GRSS) as predictors of alcohol use trajectories.

Results: Severity of exposure interacted with the GRSS to predict both intercept (12-month follow up quantity of alcohol use) and growth rate.

Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students.

Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h.

Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms.

Background: Alcohol dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified.

Methods: We conducted a genomewide association study in 706 related AD cases and 1,748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent.

JEPEGMIX: gene-level joint analysis of functional SNPs in cosmopolitan cohorts.

Motivation: To increase detection power, gene level analysis methods are used to aggregate weak signals. To greatly increase computational efficiency, most methods use as input summary statistics from genome-wide association studies (GWAS). Subsequently, gene statistics are constructed using linkage disequilibrium (LD) patterns from a relevant reference panel.

Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence.

Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.

DISTMIX: direct imputation of summary statistics for unmeasured SNPs from mixed ethnicity cohorts.

Motivation: To increase the signal resolution for large-scale meta-analyses of genome-wide association studies, genotypes at unmeasured single nucleotide polymorphisms (SNPs) are commonly imputed using large multi-ethnic reference panels. However, the ever increasing size and ethnic diversity of both reference panels and cohorts makes genotype imputation computationally challenging for moderately sized computer clusters. Moreover, genotype imputation requires subject-level genetic data, which unlike summary statistics provided by virtually all studies, is not publicly available.

JEPEG: a summary statistics based tool for gene-level joint testing of functional variants.

Motivation: Gene expression is influenced by variants commonly known as expression quantitative trait loci (eQTL). On the basis of this fact, researchers proposed to use eQTL/functional information univariately for prioritizing single nucleotide polymorphisms (SNPs) signals from genome-wide association studies (GWAS). However, most genes are influenced by multiple eQTLs which, thus, jointly affect any downstream phenotype.

Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults.

Posttraumatic stress disorder (PTSD) is a moderately heritable anxiety disorder that may develop after exposure to trauma. However, only few genetic variants that relate to PTSD have been studied. This study examined the relationship between 12 single nucleotide polymorphisms (SNPs) in the corticotropin-releasing hormone receptor 1 gene (CRHR1) and post-disaster PTSD symptoms and diagnosis in adults exposed to 2004 Florida hurricanes.

Using genetic information from candidate gene and genome-wide association studies in risk prediction for alcohol dependence.

Family-based and genome-wide association studies (GWAS) of alcohol dependence (AD) have reported numerous associated variants. The clinical validity of these variants for predicting AD compared with family history information has not been reported. Using the Collaborative Study on the Genetics of Alcoholism (COGA) and the Study of Addiction: Genes and Environment (SAGE) GWAS samples, we examined the aggregate impact of multiple single nucleotide polymorphisms (SNPs) on risk prediction.

Detecting miRNAs in deep-sequencing data: a software performance comparison and evaluation.

Deep sequencing has become a popular tool for novel miRNA detection but its data must be viewed carefully as the state of the field is still undeveloped. Using three different programs, miRDeep (v1, 2), miRanalyzer and DSAP, we have analyzed seven data sets (six biological and one simulated) to provide a critical evaluation of the programs performance. We selected these software based on their popularity and overall approach toward the detection of novel and known miRNAs using deep-sequencing data.

Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa-miR-137.

MicroRNAs (miRNAs) are small non-coding RNAs that mainly function as negative regulators of gene expression (Lai, 2002) and have been shown to be involved in schizophrenia etiology through genetic and expression studies (Burmistrova et al., 2007; Hansen et al., 2007a; Perkins et al.

MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders.

MicroRNAs (miRNAs) are a large family of small non-coding RNAs which negatively control gene expression at both the mRNA and protein levels. The number of miRNAs identified is growing rapidly and approximately one-third is expressed in the brain where they have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. Here we investigated the expression of 667 miRNAs (miRBase v.

Variants in nicotinic acetylcholine receptors alpha5 and alpha3 increase risks to nicotine dependence.

Nicotinic acetylcholine receptors bind to nicotine and initiate the physiological and pharmacological responses to tobacco smoking. In this report, we studied the association of alpha5 and alpha3 subunits with nicotine dependence and with the symptoms of alcohol and cannabis abuse and dependence in two independent epidemiological samples (n = 815 and 1,121, respectively). In this study, seven single nucleotide polymorphisms were genotyped in the CHRNA5 and CHRNA3 genes.

Cannabinoid receptor 1 gene association with nicotine dependence.

Context: The endogenous cannabinoid system has been implicated in drug addiction in animal models. The cannabinoid receptor 1 (CNR1) gene is 1 of the 2 receptors expressed in the brain. It has been reported to be associated with alcoholism and multiple drug abuse and dependence.

MEGF10 association with schizophrenia.

Background: The 5q21-31 region has been implicated as harboring risk genes for schizophrenia in many linkage studies. In our previous report of stepwise fine mapping of this region, the MEGF10 gene was one of the genes showing consistent associations in our screening subsample. In this study, we carried out independent replication and expression studies of the MEGF10 gene.