Genome-Wide Scan for Genetic Variants Associated with Early Onset Prostate Cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338514 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:<p>This is a genome-wide association scan of 931 early-onset prostate cancer cases of European ancestry. The samples were selected from prostate cancer studies at the University of Michigan. Controls were previously genotyped individuals selected from the Cancer Genetics Markers of Susceptibility (CGEMS) and Illumina's iControlDB database.</p>
| phs001185 | dbGaP
Project description: Not available
| S-EPMC3989171 | biostudies-literature
Project description:Genome-Wide Scan for Genetic Variants Associated with Early Onset Prostate Cancer
| PRJNA338515 | ENA
Project description:Prostate cancer (PrCa) manifests substantial variation in incidence rates among distinct populations. African American (AA) men are more likely to be diagnosed with and die from PrCa than European American (EA) men. Despite ongoing advancements in identifying polygenic risk variants from large genome-wide association study (GWAS) cohorts, the genetic mechanisms underlying the higher prevalence of PrCa in AA men remain unclear. A systematic approach that does not rely on extensive cohorts to identify causal regulatory variants contributing to PrCa development is still lacking. Here, by employing a sequence-based deep learning model of prostate regulatory enhancers, we identified ~2,000 essential SNPs (eSNPs) with increased alternative allele frequency in AA and which potentially affect the enhancer function leading to greater PrCa susceptibility. The identified eSNPs potentially mediate PrCa development through two complementary mechanisms: alternative alleles with increased enhancer activity are associated with immune system suppression, while those with decreased enhancer activity are linked to differentiation processes. Interestingly, the eSNPs disrupt the binding of key prostate transcription factors including FOX, AR and HOX families, collectively contributing to PrCa predisposition. Together these eSNPs can be used to assess polygenic risk score that is more effective than previous GWAS-based risk scores in distinguishing individuals with PrCa from the control.
2025-08-19 | GSE276748 | GEO
Project description:The hereditary spastics paraplegias (HSPs) are a group of over 80 neurogenetic disorders that share the feature of progressive lower limb spasticity. Bi-allelic loss-of-function variants in the RINT1 gene have been implicated in acute liver failure in the pediatric population, and were recently described to lead to a complex form of HSP in three children with early-onset spastic paraplegia, ataxia, optic nerve hypoplasia with significant vision impairment, dysmorphic features, and a thin corpus callosum. We read the article by Launay et al. with great interest and would like to add a fourth case due to novel biallelic RINT1 variants presenting with a largely ‘pure’ form of HSP including one missense variant and one splice site variant identifier by whole genome sequencing.
2025-08-31 | GSE270806 | GEO
Project description:Dissecting biopathways unveiled by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson’s disease (PD) and neurodegeneration, hence catalyzing the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and human neurodegeneration. We found that biallelic PSMF1 missense and loss-of-function variants cosegregate with phenotypes from early-onset PD and parkinsonism to perinatal lethal neurodegeneration across 15 unrelated pedigrees with 22 affected subjects, showing clear-cut genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models of psmf1 knockdown Drosophila and conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest that mitochondrial dysfunction contributes to neuronal loss.
2026-03-03 | PXD053147 | Pride
Project description:Early Onset Malignancies Initiative
| PRJNA597502 | ENA
Project description:Early Onset Malignancies Initiative
| PRJNA597501 | ENA
Project description:The spliced variant forms of androgen receptor (AR-Vs) have been identified recently in castration-resistant prostate cancer (CRPC) cell lines and clinical samples. Here we identified the cistrome and transcriptome landscape of AR-Vs in CRPC cell lines and determine the clinical significance of AR variants regulated gene.The AR variants binding sites can be identified in 22Rv1 cell line in the absence of androgen. Knocking down full-length AR (AR-FL) doesn't affect AR-Vs binding sites in genome-wide. A set of genes were identified to be regulated uniquely by AR-Vs, but not by AR-FL in androgen-depleted condition. Integrated analysis showed that some genes may be modulated by AR-Vs directly. Unsupervised clustering analysis demonstrated that AR variants gene signature can separate not only the benign and malignant prostate tissue, but also the localized prostate cancer and metastatic CRPC specimens. Some genes modulated uniquely by AR variants were also identified to correlate with the Gleason Pattern of prostate cancer and PSA failure. We conclude that AR spliced variants bind to DNA independent of full-length AR, and can modulate a unique set of genes which is not regulated by full-length AR in the absence of androgen. AR variants gene signature correlate with CRPC and prostate cnacer disease progress. Androgen receptor (AR) binding sites in human prostate cancer 22Rv1 cell lines were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.
2014-09-10 | E-GEOD-58478 | biostudies-arrayexpress
Project description:Novel Bi-Allelic Variants in RINT1 Presenting As Early-Onset Pure Hereditary Spastic Paraplegia
| PRJNA1128538 | ENA