Evaluating the Role of Interleukin 1 Beta in Mesial Temporal Lobe Epilepsy by candidate SNPs
Ontology highlight
ABSTRACT:
INSTRUMENT(S): AB 3130 Genetic Analyzer
ORGANISM(S): Homo Sapiens
SUBMITTER: UNICAMP
PROVIDER: PRJEB44301 | EVA | 2021-04-17
REPOSITORIES: EVA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Secolin_IL1B_genotypes_EVA_13apr2021.vcf.gz | Vcf | |||
| Secolin_IL1B_genotypes_EVA_13apr2021.vcf.gz.tbi | Vcf |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:The majority of single nucleotide polymorphisms (SNPs) associated with insulin resistance (IR)-relevant phenotypes by genome-wide association studies (GWASs) are located in noncoding regions, complicating their functional interpretation. Here, we utilized an adapted STARR-seq to systematically detect regulatory activity of 5,987 noncoding GWASs SNPs in three IR-relevant cell lines. We identified 876 SNPs with biased allelic enhancer activity across 133 loci, and further uncovered the genetic regulatory mechanisms underlying functional SNPs through integrating multi-omics analyses.
2023-07-28 | GSE198047 | GEO
Project description:Profiles of sequence variants that influence gene transcription are very important for understanding mechanisms that affect phenotypic variation and disease susceptibility. Using genotypes at 1.4 million SNPs and a comprehensive transcriptional profile of 15,454 coding genes and 6,113 lincRNA genes obtained from peripheral blood cells of 298 Japanese individuals, we mapped expression quantitative trait loci (eQTLs). We identified 3,804 cis-eQTLs (within 500 kb from target genes) and 165 trans-eQTLs (>500 kb away or on different chromosomes). Cis-eQTLs were often located in transcribed or adjacent regions of genes; among these regions, 5’ untranslated regions and 5’ flanking regions had the largest effects. Epigenetic evidence for regulatory potential accumulated in public databases explained the magnitude of the effects of our eQTLs. Cis-eQTLs were often located near the respective target genes, if not within genes. Large effect sizes were observed with eQTLs near target genes, and effect sizes were obviously attenuated as the eQTL distance from the gene increased. Using a very stringent significance threshold, we identified 165 large-effect trans-eQTLs. We used our eQTL map to assess 8,069 disease-associated SNPs identified in 1,436 genome-wide association studies (GWAS). We identified genes that might be truly causative, but GWAS might have failed to identify for 148 out of the GWAS-identified SNPs; for example, TUFM (P=3.3E-48) was identified for inflammatory bowel disease (early onset); ZFP90 (P=4.4E-34) for ulcerative colitis; and IDUA (P=2.2E-11) for Parkinson's disease. We identified four genes (P<2.0E-14) that might be related to three diseases and two hematological traits; each expression is regulated by trans-eQTLs on a different chromosome than the gene. The study subjects were 301 apparently healthy individuals residing in Nagahama City, Japan. Whole blood was collected from each participant when in a non-stimulated state.
2014-06-23 | E-GEOD-53351 | biostudies-arrayexpress
Project description:Profiles of sequence variants that influence gene transcription are very important for understanding mechanisms that affect phenotypic variation and disease susceptibility. Using genotypes at 1.4 million SNPs and a comprehensive transcriptional profile of 15,454 coding genes and 6,113 lincRNA genes obtained from peripheral blood cells of 298 Japanese individuals, we mapped expression quantitative trait loci (eQTLs). We identified 3,804 cis-eQTLs (within 500 kb from target genes) and 165 trans-eQTLs (>500 kb away or on different chromosomes). Cis-eQTLs were often located in transcribed or adjacent regions of genes; among these regions, 5’ untranslated regions and 5’ flanking regions had the largest effects. Epigenetic evidence for regulatory potential accumulated in public databases explained the magnitude of the effects of our eQTLs. Cis-eQTLs were often located near the respective target genes, if not within genes. Large effect sizes were observed with eQTLs near target genes, and effect sizes were obviously attenuated as the eQTL distance from the gene increased. Using a very stringent significance threshold, we identified 165 large-effect trans-eQTLs. We used our eQTL map to assess 8,069 disease-associated SNPs identified in 1,436 genome-wide association studies (GWAS). We identified genes that might be truly causative, but GWAS might have failed to identify for 148 out of the GWAS-identified SNPs; for example, TUFM (P=3.3E-48) was identified for inflammatory bowel disease (early onset); ZFP90 (P=4.4E-34) for ulcerative colitis; and IDUA (P=2.2E-11) for Parkinson's disease. We identified four genes (P<2.0E-14) that might be related to three diseases and two hematological traits; each expression is regulated by trans-eQTLs on a different chromosome than the gene.
2014-06-23 | GSE53351 | GEO
Project description:Background: Expression quantitative trait loci (eQTL) studies are a valuable approach for identifying genetic variants correlated with gene expression. However, identifying the causal variants is challenging due to linkage disequilibrium amongst variants in the same haplotype block. In this study, we aim to identify functional SNPs in key regulatory regions that alter transcriptional regulation and thus, potentially impact cellular function. The majority of disease-associated single-nucleotide polymorphisms (SNPs) are located in regulatory regions, which can result in allele-specific binding (ASB) of transcription factors and differential expression of the target gene alleles. Here, we present regSNPs-ASB, a generalized linear model-based approach to accurately identify regulatory SNPs that are located in transcription factor binding sites from ATAC-seq data. Results: Using regSNPs-ASB, we identified 53 regulatory SNPs in human MCF-7 breast cancer cells and 125 regulatory SNPs in human mesenchymal stem cells (MSC). By integrating the regSNPs-ASB output with RNA-seq experimental data and publicly available chromatin interaction data from MCF-7 cells, we found that these 53 regulatory SNPs were associated with 74 potential target genes and that 32 (43%) of these genes showed significant allele-specific expression (ASE). By comparing all of the MCF-7 and MSC regulatory SNPs to the eQTLs in the Genome-Tissue Expression (GTEx) Project database, we found that 30% (16/53) of the regulatory SNPs in MCF-7 and 43% (52/122) of the regulatory SNPs in MSC were also eQTLs. The enrichment of regulatory SNPs in eQTLs indicated that many of them are likely responsible for allelic differences in gene expression (chi-square test, p-value < 0.01). In sum, we conclude that regSNPs-ASB is a useful tool for identifying causal variants from ATAC-seq data. This new computational tool will enable efficient prioritization of genetic variants identified as eQTL for further studies to validate their causal regulatory function. Ultimately, identifying causal genetic variants will further our understanding of the underlying molecular mechanisms of disease and the eventual development of potential therapeutic targets.
2020-02-14 | GSE145245 | GEO
Project description:Neuroendocrine prostate cancer is an aggressive disease characterized by early metastasis, drug resistance and poor prognosis. Genome-wide association studies (GWAS) previously identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer. SNP rs11067228 as a significant variant associated with castration-resistant metastasis (CM) in prostate cancer (PCa). However, mechanisms underlying activity of the rs11067228 risk variant remain unclear. Here, we demonstrated that risk SNP rs11067228 is located in an H3K27ac-enriched active enhancer, and that activity of that region affects castration-resistance and neuroendocrine differentiation in PCa cells. We identified the RNA-splicing factor SRRM4 as a functional target gene as shown in both cell line and xenograft model. In addition, overexpression of SRRM4 is sufficient to induce PCa cell drug resistance and neuroendocrine differentiation. Moreover, site-directed mutation of the rs11067228 non-risk G to the risk A allele enabled binding of the transcription factor SOX4, activating candidate target gene expression. Taken together, our findings indicated that the rs11067228-associated enhancer modulates expression of SRRM4 via allele-specific long-range chromatin interactions, thereby governing PCa drug resistance and neuroendocrine differentiation.
2026-02-09 | PXD055628 | Pride
Project description:Genome-wide association studies (GWAS) have identified thousands of single nucleotide polymorphisms (SNPs) associated with different human phenotypes. Most SNPs are located in non-coding regions of the genome, where a small subset of causal SNPs is thought to contribute to risk by regulating transcription. However, identification of such causal variants remains challenging due to linkage disequilibrium, where blocks of SNPs are inherited together. Here, we performed a massively parallel reporter assay called survey of regulatory elements (SuRE) in human neural stem cells to assess the transcription regulatory potential of 7.1 million SNPs. We identified 7,002 SNPs with regulatory potential (reporter assay quantitative trait loci, raQTLs), thereby increasing the number of putative regulatory variants in neural cell types by one order of magnitude. raQTLs were enriched for enhancers and often coincide with binding sites for transcription factors, such as ZBTB33, YY1, and ETS factors. Overlapping SuRE data with eQTL data pinpointed likely gene-regulatory variants. Overlap with GWAS for seven neuropsychiatric phenotypes identified 187 raQTLs in risk loci containing 183,186 SNPs assessed by SuRE. In conclusion, our SuRE dataset provides a rich source to prioritize genetic variants that may be relevant for disease.
2026-01-31 | GSE292348 | GEO
Project description:The expression of TWEAK and Fn14 was increased in early skin lesions of SSc patients. Fn14 expression on human dermal fibroblasts is significantly increased after stimulation with serum from patients with systemic sclerosis. The interplay between TWEAK and Fn14 is pivotal in the fibrotic progression of various autoimmune diseases. These observations implicate the TWEAK/Fn14 signaling pathway may as a critical player in the pathological advancement of systemic sclerosis; however, the precise underlying mechanisms require further clarification. Thus, human dermal fibroblasts were stimulated by serum from systemic sclerosis patients, and with or without the addition of Fn14 antagonists. We then assessed the antifibrotic effects of this antagonist through RNA sequencing, and preliminary exploration of possible molecular mechanisms.
2024-08-05 | GSE273556 | GEO
Project description:Inflammatory bowel disease (IBD) is a common and chronic gut disorder, with two subtypes: Crohn's disease (CD) and ulcerative colitis (UC), which are challenging to diagnose. The molecular pathology IBD is not well understood, and the underlying gene regulatory regions have not been comprehensively investigated. Relatedly, most IBD-associated SNPs are located in non-coding regions, and may effect gene regulation. Here, we profiled genome-wide promoter and enhancer activity in the descending colon of IBD patients. IBD-induced enhancer and promoters are highly enriched for IBD-associated SNPs, and can predict IBD diagnosis with an accuracy of 85% in an external cohort.
2018-03-14 | GSE95437 | GEO
Project description:ApoC-III is a proatherogenic protein associated with elevated triglycerides; its deficiency is associated with reduced atherosclerosis. Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy. We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Association between genotyed SNPs and APOC3 response to therapy was conducted
2012-01-11 | GSE34945 | GEO
Project description:Genome-wide association studies (GWASs) have identified thousands of single nucleotide polymorphisms (SNPs) associated with human traits and diseases. But because the vast majority of these SNPs are located in the noncoding regions of the genome their risk promoting mechanisms are elusive. Employing a new methodology combining cistromics, epigenomics and genotype imputation we annotate the noncoding regions of the genome in breast cancer cells and systematically identify the functional nature of SNPs associated with breast cancer risk. Our results demonstrate that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of H3K4me1 in a cancer and cell-type-specific manner. Furthermore, the majority of these risk-associated SNPs modulate the affinity of chromatin for FOXA1 at distal regulatory elements, which results in allele-specific gene expression, exemplified by the effect of the rs4784227 SNP on the TOX3 gene found within the 16q12.1 risk locus. Examination of histone modification H3K4me2 in untreated and E2 treated cells
2012-08-17 | E-GEOD-31151 | biostudies-arrayexpress