Project description:We have combined high-quality genome sequencing and RNA-sequencing data within a 17-individual, three generation family. Using these data, we have contrasted cis-acting expression, allele-specific expression and splicing quantitative trait loci (collectively termed eQTLs) within the family to eQTLs discovered within a cell-type and ethnicity-matched population sample. We identified that eQTL that exhibit larger effects in the family compared to the population are enriched for rare regulatory and splicing variants and were more likely to influence essential genes. In addition, we identify several large effect-size eQTLs within the family for genes involved in complex disease. Through analysis of eQTLs in a large family we also report the utility of non-coding genome annotation to predicting the effect of rare non-coding variants. We find that a combination of distance to the transcription start site, evolutionary constraint and epigenetic annotation is considerably more informative for predicting the consequence of rare non-coding variants than for common variants. In summary, through transcriptome analyses within a large family we are able to identify the contribution of rare non-coding variants to expression phenotypes and further demonstrate the predictive potential of diverse non-coding genome annotation for interpretation of the impact of rare non-coding variants. RNA-Sequencing of CEPH/UTAH family 1463
Project description:<p>The goal of the project is to identify genes that make individuals more susceptible to bipolar disorder (manic depressive illness) and to better understand the brain pathways involved in the disease.</p> <p><b>Dataset versioning</b><br/> <ul> <li>Version 1: European-American (EA) ancestry only</li> <li>Version 2: Version 1 plus African-American (AA) ancestry</li> <li>Version 3: EA and AA samples plus updated diagnostic criteria</li> </ul> </p> <p><b>Consent groups and participant set</b><br/> <ul> <li>General research use (GRU): 1767 controls (1081 EA controls, 686 AA controls)<br/> This consent group includes all controls for the Bipolar study, which are a subset of controls for the Schizophrenia study (subset of Schizophrenia: GRU).</li> <li>Bipolar and related disorders (BARD): 841 cases (691 EA cases, 150 AA cases)<br/> This consent group includes a subset of the Bipolar cases.</li> <li>Bipolar disorder only (BDO): 653 cases (388 EA cases, 265 AA cases)<br/> This consent group includes a subset of the Bipolar cases.</li> </ul> </p>
Project description:Bipolar disorder (BD) is a highly heritable and heterogeneous mental illness whose manifestations often include impulsive and risk-taking behavior. This particular phenotype suggests that abnormal striatal function could be involved in BD etiology, yet most transcriptomic studies of this disorder have concentrated on cortical brain regions. We report the first transcriptome profiling by RNA-Seq of the human dorsal striatum comparing bipolar and control subjects. Differential expression analysis and functional pathway enrichment analysis were performed to identify changes in gene expression that correlate with BD status. Further co-expression and enrichment analyses were performed to identify sets of correlated genes that show association to BD. Total RNA samples were isolated from 36 postmortem dorsal striatum subjects (18 bipolar and 18 control) and sequenced. One outlier sample was removed and 35 samples (18 bipolar and 17 control) were analyzed.
Project description:Analysis of gene-expression changes in depressed subjects with bipolar disorder compared to healthy controls. Results provide information on pathways that may be involved in the pathogenesis of bipolar depression. Total RNA isolated from PAXgene blood RNA tubes from 20 depressed subjects with bipolar disorder and 15 healthy controls.
Project description:Bipolar disorder (BD) is a psychiatric disorder in which the core feature is pathological disturbance in mood ranging from extreme elation (mania) to severe depression. Study has shown an aberrant pro-inflammatory status of monocytes/macrophages in mood disorders. Therefore, this study aimed at studying the monocyte compartment in Bipolar Disorder, by transcription profiling of CD14+ monocytes in patients and controls.