Exome Genotyping Study of Scripps Venous Thrombosis Registry using Axiom® Exome Genotyping Array
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76016 | GEO | 2021/12/04
REPOSITORIES: GEO
Similar Datasets
Project description:Cerebrospinal fluid (CSF) is virtually the only one accessible source of proteins derived from the central nervous system (CNS) of living humans and possibly reflects the pathophysiology of a variety of neuropsychiatric diseases. However, little is known regarding the genetic basis of variation in protein levels of human CSF. We examined CSF levels of 1,126 proteins in 133 subjects and performed genome-wide association analysis of 514,227 single nucleotide polymorphisms (SNPs) to detect protein quantitative trait loci (pQTLs). Spearman’s correlation was used to identify association between genotypes of SNPs and protein levels. A total of 421 cis and 25 trans SNP-protein pairs were significantly correlated at a false discovery rate (FDR) of less than 0.01 (nominal P < 7.66 x 10 −9). Cis-only analysis revealed additional 580 significant cis SNP-protein pairs with FDR < 0.01 (nominal P < 2.13 x 10 −5). pQTL SNPs were more likely, compared to non-pQLT SNPs, to be disease/trait-associated variants identified by previous genome-wide association studies. The present findings suggest that genetic variations play a major role in the regulation of protein expression in the CNS. The obtained database will serve as a valuable resource for future neuropsychiatric research.
2016-12-30 | GSE83709 | GEO
Project description:Cerebrospinal fluid (CSF) is virtually the only one accessible source of proteins derived from the central nervous system (CNS) of living humans and possibly reflects the pathophysiology of a variety of neuropsychiatric diseases. However, little is known regarding the genetic basis of variation in protein levels of human CSF. We examined CSF levels of 1,126 proteins in 133 subjects and performed genome-wide association analysis of 514,227 single nucleotide polymorphisms (SNPs) to detect protein quantitative trait loci (pQTLs). Spearman’s correlation was used to identify association between genotypes of SNPs and protein levels. A total of 421 cis and 25 trans SNP-protein pairs were significantly correlated at a false discovery rate (FDR) of less than 0.01 (nominal P < 7.66 x 10 −9). Cis-only analysis revealed additional 580 significant cis SNP-protein pairs with FDR < 0.01 (nominal P < 2.13 x 10 −5). pQTL SNPs were more likely, compared to non-pQLT SNPs, to be disease/trait-associated variants identified by previous genome-wide association studies. The present findings suggest that genetic variations play a major role in the regulation of protein expression in the CNS. The obtained database will serve as a valuable resource for future neuropsychiatric research.
2016-12-30 | GSE83708 | GEO
Project description:Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. We studied 134 patients with VTE separated into 3 groups: (1) ‘low-risk’ patients had ≥1 provoked VTE; (2) ‘moderate-risk’ patients had no more than 1 unprovoked VTE; (3) ‘high-risk’ patients had ≥2 unprovoked VTE. 44 individuals with no history of VTE were enrolled as healthy controls. Consented individuals were enrolled at 4 medical centers in the US. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Using class prediction analysis, we distinguished high-risk patients from healthy controls with good receiver operating curve characteristics (AUC=0.88). We also distinguished high-risk from low-risk individuals, moderate-risk individuals from healthy controls, and low-risk individuals from healthy controls with AUC’s of 0.72, 0.77 and 0.72, respectively. Using differential expression analysis, we identified genes relevant to coagulation, immune response and vascular biology, such as SELP and CD46, which were differentially expressed in at least two comparisons. Neither approach distinguished the moderate-risk patients from the high-risk or low-risk groups. Gene expression profiles may provide insights into biological mechanisms associated with patients at risk for recurrent VTE. Prospective studies are needed to validate these findings.
2015-11-23 | GSE48000 | GEO
Project description:Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. We studied 134 patients with VTE separated into 3 groups: (1) âlow-riskâ patients had â¥1 provoked VTE; (2) âmoderate-riskâ patients had no more than 1 unprovoked VTE; (3) âhigh-riskâ patients had â¥2 unprovoked VTE. 44 individuals with no history of VTE were enrolled as healthy controls. Consented individuals were enrolled at 4 medical centers in the US. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. Using class prediction analysis, we distinguished high-risk patients from healthy controls with good receiver operating curve characteristics (AUC=0.88). We also distinguished high-risk from low-risk individuals, moderate-risk individuals from healthy controls, and low-risk individuals from healthy controls with AUCâs of 0.72, 0.77 and 0.72, respectively. Using differential expression analysis, we identified genes relevant to coagulation, immune response and vascular biology, such as SELP and CD46, which were differentially expressed in at least two comparisons. Neither approach distinguished the moderate-risk patients from the high-risk or low-risk groups. Gene expression profiles may provide insights into biological mechanisms associated with patients at risk for recurrent VTE. Prospective studies are needed to validate these findings. This study includes a total of 218 samples/individuals (in 5 groups; APS, high-risk VTE, moderate-risk VTE, low-risk VTE and healthy-controls). Samples in which the percent of probes present was 15% or less (n=51) were excluded leaving 167 samples. The data for these 167 samples were normalized together. However, this record represents the 132 individual samples in the following groups; high-risk (n=40); moderate-risk (n=33); low-risk (n=34); and healthy controls (n=25). The 35 samples in APS group are represented in GSE48001.
2015-11-23 | E-GEOD-48000 | biostudies-arrayexpress
Project description:Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Pulmonary embolism is a life threatening manifestation of VTE that occurs in at least half the patients on presentation. In addition, VTE recurs in up to 30% of patients after a standard course of anticoagulation, and there is not a reliable way of predicting recurrence. We investigated whether gene expression profiles of whole blood could distinguish patients with VTE from healthy controls, single VTE from those with recurrence, and DVT alone from those with PE. 70 adults with VTE on warfarin and 63 healthy controls were studied. Patients with antiphospholipid syndrome or cancer were excluded. Blood was collected in PAXgene tubes, RNA isolated, and gene expression profiles obtained using Affymetrix arrays. We developed a 50 gene model that distinguished healthy controls from subjects with VTE with excellent receiver operating characteristics (AUC 0.94; P < 0.0001). We also discovered a separate 50 gene model that distinguished subjects with a single VTE from those with recurrent VTE with good receiver operating characteristics (AUC 0.75; P=0.008). In contrast, we were unable to distinguish subjects with DVT from those with PE using gene expression profiles. Gene expression profiles of whole blood can distinguish subjects with VTE from healthy controls and subjects with a single VTE from those with recurrence. Additional studies should be performed to validate these results and develop diagnostic tests. Gene expression profiling is likely translatable to other thrombotic disorders(e.g., patients with cancer and VTE).
2011-11-10 | GSE19151 | GEO
Project description:Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Pulmonary embolism is a life threatening manifestation of VTE that occurs in at least half the patients on presentation. In addition, VTE recurs in up to 30% of patients after a standard course of anticoagulation, and there is not a reliable way of predicting recurrence. We investigated whether gene expression profiles of whole blood could distinguish patients with VTE from healthy controls, single VTE from those with recurrence, and DVT alone from those with PE. 70 adults with VTE on warfarin and 63 healthy controls were studied. Patients with antiphospholipid syndrome or cancer were excluded. Blood was collected in PAXgene tubes, RNA isolated, and gene expression profiles obtained using Affymetrix arrays. We developed a 50 gene model that distinguished healthy controls from subjects with VTE with excellent receiver operating characteristics (AUC 0.94; P < 0.0001). We also discovered a separate 50 gene model that distinguished subjects with a single VTE from those with recurrent VTE with good receiver operating characteristics (AUC 0.75; P=0.008). In contrast, we were unable to distinguish subjects with DVT from those with PE using gene expression profiles. Gene expression profiles of whole blood can distinguish subjects with VTE from healthy controls and subjects with a single VTE from those with recurrence. Additional studies should be performed to validate these results and develop diagnostic tests. Gene expression profiling is likely translatable to other thrombotic disorders(e.g., patients with cancer and VTE). 70 adults with one or more prior VTE on warfarin and 63 healthy controls were studied. Patients with antiphospholipid syndrome or cancer were excluded. Blood was collected in PAXgene tubes, RNA isolated, and gene expression profiles obtained using Affymetrix arrays.
2011-11-10 | E-GEOD-19151 | biostudies-arrayexpress
Project description:Background: Patients with high-grade gliomas are at high risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) are small non-coding RNAs with multiple roles in tumor biology, hemostasis and platelet function. We aimed to explore the association between plasma miRNAs and risk of VTE in high-grade glioma. Results: We conducted a nested-case control study within 152 patients with WHO grade IV glioma that had been included in the Vienna Cancer and Thrombosis Study (CATS), a prospective cohort study focused on risk factors for VTE in newly diagnosed or recurrent cancer. At study inclusion a single blood draw was taken, and patients were thereafter followed for a maximum of two years. During that time, 24 patients (16%) developed VTE. Of the other 128 patients, we randomly selected 24 age- and sex-matched controls. After sample quality control, the final group size was 21 VTE-patients and 23 without VTE. Small RNA next-generation sequencing of plasma was performed. We observed that hsa-miR-451a was globally the most abundant miRNA. Notably, 51% of all miRNAs showed a correlation with platelet count. The analysis of miRNAs differentially regulated in VTE patients – with and without platelet adjustment – identified potential VTE biomarker candidates such as has-miR- 221-3p. Conclusion: We here provide one of the largest and deepest peripheral blood miRNA datasets of high-grade glioma patients so far. Further, we confirm previous observations of a considerable impact of platelet count on the blood miRNome. And, finally, we present first VTE biomarker candidates that can serve as the starting point for future confirmatory research.
2023-12-31 | GSE222666 | GEO
Project description:Multiple common variants for celiac disease influencing immune gene expression The goal of this study was to study the effect of genetic variation on gene expression of untouched primary leucocytes. We obtained peripheral blood RNA from unrelated Dutch individuals using PAXgene tubes. We performed a second-generation genome wide association study of 4,533 celiac disease cases and 10,750 controls. We genotyped 113 selected SNPs with PGWAS<10-4, and 18 SNPs from 14 known loci, in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome wide significance (Pcombined<5x10-8), most contain immune function genes (BACH2, CCR4, CD80, CIITA/SOCS1/CLEC16A, ICOSLG, ZMIZ1) with ETS1, RUNX3, THEMIS and TNFRSF14 playing key roles in thymic T cell selection. A further 13 regions had suggestive association evidence. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P<0.0028, FDR 5%) with cis gene expression. *** Due to privacy concerns, the SNP data is not available with unrestricted access. Individuals wishing to obtain this data for research purposes may request access directly from the submitter (contact info below). ***
2010-02-28 | GSE20142 | GEO
Project description:Multiple common variants for celiac disease influencing immune gene expression The goal of this study was to study the effect of genetic variation on gene expression of untouched primary leucocytes. We obtained peripheral blood RNA from unrelated Dutch and UK individuals using PAXgene tubes. We performed a second-generation genome wide association study of 4,533 celiac disease cases and 10,750 controls. We genotyped 113 selected SNPs with PGWAS<10-4, and 18 SNPs from 14 known loci, in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome wide significance (Pcombined<5x10-8), most contain immune function genes (BACH2, CCR4, CD80, CIITA/SOCS1/CLEC16A, ICOSLG, ZMIZ1) with ETS1, RUNX3, THEMIS and TNFRSF14 playing key roles in thymic T cell selection. A further 13 regions had suggestive association evidence. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P<0.0028, FDR 5%) with cis gene expression. *** Due to privacy concerns, the SNP data is not available with unrestricted access. Individuals wishing to obtain this data for research purposes may request access directly from the submitter (contact info below). ***
2010-02-28 | GSE20332 | GEO
Project description:Despite the large amounts of transcriptome data generated for many non-model organisms, there has been a much lesser uptake of individual genomic sequencing for detecting SNPs and determining haplotypes in these species. Transcriptome data represents a source of variant information, specifically for coding DNA, however there is little information on the accuracy, coverage and limitations of using transcriptomic data for the identification of single nucleotide polymorphisms (SNPs) in non-model organisms. To investigate this, we generated the first whole exome design for bovine using the Roche Nimblegen Developer system (Roche, USA) and used it to sequence and call SNPs from a lactating dairy cow model with genetically divergent fertility phenotypes (Fert+, n=8; Fert-, n=8). We compared these results to SNPs called from liver and muscle transcriptomes from the same animals. Our exome demonstrated 99.1% coverage of the target design of 56.7MB, whereas the transcriptomes only covered 60 and 54.5% of 44.2 and 42.8MB in liver and muscle respectively. We found that specificity of SNP detection in the transcriptome data is ~75% following basic hard-filtering, but could be increased marginally to ~80% by increasing the minimum threshold of reads covering a SNP, and number of samples in which it was found. Functional annotation of non-synonymous SNPs specific to both the high and low fertility phenotype identified immune response-related genes, supporting previous work that identified this process as key to the phenotype.
2015-10-08 | GSE62160 | GEO