RareBliss: Rare Bipolar Loci Identification Through Sequencing Study
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PROVIDER: PRJNA383281 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:RareBliss: Rare Bipolar Loci Identification Through Sequencing Study
| PRJNA383282 | ENA
Project description:Rare loss-of-function (LoF) mutations in SETD1A are associated with schizophrenia (SCZ). However, how SETD1A haploinsufficiency leads to SCZ-associated phenotypes and its relevance to patients without these rare mutations is unknown. Here, we identify SETD1A bound loci and regulated genes in human prenatal cortex and isogenic pluripotent stem cell-derived neuronal models engineered with SETD1A LoF variants, including the most common patient mutation. SETD1A preferentially binds the promoters of SCZ and Bipolar risk loci that regulate chromatin remodeling, DNA repair, and synaptic function. Additionally, SETD1A binds to DNA damage prone sites in neural progenitor cells and postmitotic neurons. SETD1A haploinsufficiency causes accelerated neurogenesis, reduced neuronal complexity, and DNA damage accumulation in postmitotic neurons that is rescued by inhibiting the H3K4me2/3 demethylase KDM5. In postmortem SCZ cortical tissue, individuals who lack SETD1A mutations exhibit reduced SETD1A expression, associated with downregulation of SETD1A-regulated genes, implicating SETD1A-H3K4me dysfunction in sporadic SCZ cases. Therefore, restoring the SETD1A-H3K4me epigenetic imbalance may benefit individuals with SETD1A haploinsufficiency as well as a broader psychiatric population without SETD1A mutations.
2025-09-15 | GSE293325 | GEO
Project description:GAIN: Whole Genome Association Study of Bipolar Disorder
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Project description:Rare loss-of-function (LoF) mutations in SETD1A are associated with schizophrenia (SCZ). However, how SETD1A haploinsufficiency leads to SCZ-associated phenotypes and its relevance to patients without these rare mutations is unknown. Here, we identify SETD1A bound loci and regulated genes in human prenatal cortex and isogenic pluripotent stem cell-derived neuronal models engineered with SETD1A LoF variants, including the most common patient mutation. SETD1A preferentially binds the promoters of SCZ and Bipolar risk loci that regulate chromatin remodeling, DNA repair, and synaptic function. Additionally, SETD1A binds to DNA damage prone sites in neural progenitor cells and postmitotic neurons. SETD1A haploinsufficiency causes accelerated neurogenesis, reduced neuronal complexity, and DNA damage accumulation in postmitotic neurons that is rescued by inhibiting the H3K4me2/3 demethylase KDM5. In postmortem SCZ cortical tissue, individuals who lack SETD1A mutations exhibit reduced SETD1A expression, associated with downregulation of SETD1A-regulated genes, implicating SETD1A-H3K4me dysfunction in sporadic SCZ cases. Therefore, restoring the SETD1A-H3K4me epigenetic imbalance may benefit individuals with SETD1A haploinsufficiency as well as a broader psychiatric population without SETD1A mutations.
2025-09-15 | GSE293154 | GEO
Project description:Rare loss-of-function (LoF) mutations in SETD1A are associated with schizophrenia (SCZ). However, how SETD1A haploinsufficiency leads to SCZ-associated phenotypes and its relevance to patients without these rare mutations is unknown. Here, we identify SETD1A bound loci and regulated genes in human prenatal cortex and isogenic pluripotent stem cell-derived neuronal models engineered with SETD1A LoF variants, including the most common patient mutation. SETD1A preferentially binds the promoters of SCZ and Bipolar risk loci that regulate chromatin remodeling, DNA repair, and synaptic function. Additionally, SETD1A binds to DNA damage prone sites in neural progenitor cells and postmitotic neurons. SETD1A haploinsufficiency causes accelerated neurogenesis, reduced neuronal complexity, and DNA damage accumulation in postmitotic neurons that is rescued by inhibiting the H3K4me2/3 demethylase KDM5. In postmortem SCZ cortical tissue, individuals who lack SETD1A mutations exhibit reduced SETD1A expression, associated with downregulation of SETD1A-regulated genes, implicating SETD1A-H3K4me dysfunction in sporadic SCZ cases. Therefore, restoring the SETD1A-H3K4me epigenetic imbalance may benefit individuals with SETD1A haploinsufficiency as well as a broader psychiatric population without SETD1A mutations.
2025-09-15 | GSE293155 | GEO
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
2014-09-01 | E-GEOD-56961 | biostudies-arrayexpress
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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>
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