Simvastatin treated Lymphoblastoid Cell lines from Cholesterol and Pharmacogenomics (CAP) Trial
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36868 | GEO | 2012/07/01
SECONDARY ACCESSION(S): PRJNA157039
REPOSITORIES: GEO
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Project description:Statins reduce cardiovascular disease risk by lowering plasma low density lipoprotein (LDL)-cholesterol. To identify novel pathways that modulate statin response, we assessed the influence of simvastatin exposure on expression quantitative trait locus (eQTL) associations across the genome in 480 lymphoblastoid cell lines (LCLs). Cell lines were derived blood samples collected ant entry visit from participants in the Cholesterol and Pharmacogenomics (CAP) trial, who underwent a 6 week 40mg/day simvastatin trial. We identified 4590 cis-eQTLS that were independent of treatment status (FDR=1%) and six cis-eQTLS for which there was evidence of an interaction with treatment (FDR=20%). Genotypes and Phenotypes derived from these indivudals are available through dbGaP (Accession Number). eQTL results are available at: http://eqtl.uchicago.edu/cgi=bin/gbrowse/eqtl/ Dataset consists of 960 expression beadarrays (Illumina HumanRef-8v3) representing paired samples derived from 24-hour exposures of 480 lymphoblastoid cell lines (LCLs) to 2 micromolar simvastatin acid or control buffer.
2012-06-30 | E-GEOD-36868 | biostudies-arrayexpress
Project description:The goal was to study the effects of lead exposure on gene expression and identify the lead-responsive genes. After detecting 1,536 cis-eQTLs (FDR ≤ 10%) and 952 trans-eQTLs, we focused our analysis on Pb-sensitive “trans-eQTL hotspots”.
2016-06-10 | GSE83141 | GEO
Project description:Characterization of genetic variants affecting genome-wide gene expression levels (expression quantitative trait loci or eQTLs) in pig testes may improve our understanding of genetic architecture of boar taint (an animal welfare trait) and helps in genome-assisted or genomic selection programs. The aims of this study were to identify eQTLs associated with androstenone, to find candidate eQTLs for low androstenone, and to validate the top eQTL by reverse transcriptase quantitative PCR (RT-qPCR). Gene expression profiles were obtained by RNA sequencing in testis from Danish cross-bred pigs and genotype data by 80K single nucleotide polymorphism panel. A total of 262 eQTLs [false discovery rate (FDR) < 0.05] were identified by using two software packages: Matrix eQTL and Krux eQTL. Of these, 149 cis-acting eQTLs were significantly associated with androstenone concentrations and gene expression (FDR < 0.05). The eQTLs were associated with several genes of boar taint relevance including CYP1A2, CYB5D1, and SPHK2. One eQTL gene, AMPH, was differentially expressed (FDR < 0.05) and affected by chicory. Five candidate eQTLs associated with low androstenone concentrations were discovered, including the top eQTL associated with CYP1A2. RT-qPCR confirmed target gene expression to be significantly (P < 0.05) different based on eQTL genotypes. Furthermore, eQTLs were enriched as QTLs for 15 boar taint related traits from the PigQTLdb. This is the first study to report eQTLs in testes of commercial crossbred pigs used in pork production and to reveal genetic architecture of boar taint. Potential applications include development of a DNA test and in advanced genomic selection models for boar taint.
2019-08-22 | GSE114225 | GEO
Project description:The goal was to study the effects of lead exposure on gene expression and identify the lead-responsive genes. After detecting 1,536 cis-eQTLs (FDR ⤠10%) and 952 trans-eQTLs, we focused our analysis on Pb-sensitive âtrans-eQTL hotspotsâ. 158 randomly selected Drosophila Synthetic Population Resource (A2) samples (control 79 samples and Pb-treated) without replicates
2016-06-10 | E-GEOD-83141 | biostudies-arrayexpress
Project description:The aim of our study was to assess the impact of simvastatin on the amount of cytosolic lipid droplets (LDs), which are implicated in many biological processes including proliferation, inflammation, carcinogenesis, apoptosis, necrosis or growth arrest. Human pancreatic cancer cells MiaPaCa-2 were treated with simvastatin (6 and 12 _M) for 24 hours. Changes in expression of genes related to lipid metabolism in the simvastatin-treated cells were examined by DNA microarray analysis. The treatment of the cells with simvastatin increased their intracellular content of LDs, partially due to the uptake of cholesterol and triacylglycerides from medium; but in particular, due to enhanced synthesis of triacylglycerides as proved by detection of significant overexpression of genes related to de novo synthesis of triacylglycerides and phospholipids. Further, simvastatin markedly influenced expression of genes directly affecting cell proliferation and signaling.
2013-11-21 | E-MTAB-1501 | biostudies-arrayexpress
Project description:Background: Cytokines are critical to human disease and are attractive therapeutic targets given their widespread influence on gene regulation and transcription. Defining the downstream regulatory mechanisms influenced by cytokines is central to defining drug and disease mechanisms. One promising strategy is to use interactions between expression quantitative trait loci (eQTLs) and cytokine levels to define target genes and mechanisms. Results: In a clinical trial for anti-IL-6 in patients with systemic lupus erythematosus we measured interferon (IFN) status, anti-IL-6 drug exposure and whole blood genome-wide gene expression at three time points (379 samples from 157 individuals). First, we show that repeat transcriptomic measurements increases the number of cis eQTLs identified compared to using a single time point by 64%. Then, after identifying 4,818 cis-eQTLs, we observed a statistically significant enrichment of in vivo eQTL interactions with IFN status (p<0.001 by permutation) and anti-IL-6 drug exposure (p<0.001). We observed 210 and 72 interactions for IFN and anti-IL-6 respectively (FDR<20%). Anti-IL-6 interactions have not yet been described while 99 of the IFN interactions are novel. Finally, we found transcription factor binding motifs interrupted by eQTL interaction SNPs, pointing to key regulatory mediators of these environmental stimuli and therefore potential therapeutic targets for autoimmune diseases. In particular, genes with IFN interactions are enriched for ISRE binding site motifs, while those with anti-IL-6 interactions are enriched for IRF4 motifs. Conclusion: This study highlights the potential to exploit clinical trial data to discover in vivo eQTL interactions with therapeutically relevant environmental variables.
2018-09-24 | GSE116006 | GEO
Project description:HMG-CoA reductase inhibitors, statins, have beneficial vascular effects beyond their cholesterol-lowering action. These pleiotropic effects include an anti-inflammatory effect on macrophages. Since macrophages play a central role in atherogenesis, we further characterized the effects on peripheral blood monocyte-macrophages (HPBM). Using Affymetrix gene chip analysis of simvastatin-treated HPBM, we found that simvastatin treatment lead to the downregulation of the expression of many proinflammatory genes including several chemokines (e.g. MCP-1, MIP-1 alpha and β, RANTES, several other CC and CXC chemokines, IL-2 receptor-β, and leukemia inhibitory factor), members of the tumor necrosis factor family (e.g. lymphotoxin beta and TRAIL), VCAM-1, ICAM-3, and tissue factor (TF). Simvastatin also modulated the expression of several transcription factors essential for the inflammatory response: simvastatin downregulated the expression of NF-kappaB relA/p65 subunit and ets-1 transcription factor, and upregulated the expression of a novel atheroprotective transcription factor, Kruppel-like factor 2 (KLF-2). The effects of simvastatin on KLF-2 and its target genes were dependent on protein prenylation, since inhibitors of protein prenylation had a similar inhibitory effect in THP-1 derived macrophages. Additionally, by lentiviral overexpression KLF-2 we showed that the effect of simvastatin on MCP-1 and TF were dependent on KLF-2. We concluded that simvastatin had a strong anti-inflammatory effect on macrophages, which includes upregulation of the atheroprotective transcription factor KLF-2. These findings further explain the beneficial pleiotropic effects of statins on cardiovascular diseases. Keywords: time-course, response to treatment
2006-12-31 | GSE4883 | GEO
Project description:In this study we use RNAseq to explore allele specific expression (ASE) in adipose tissue of male and female F1 mice, produced from reciprocal crosses of C57BL/6J and DBA/2J strains. Comparison of the identified cis-eQTLs, to local-eQTLs, that were obtained from adipose tissue expression in two previous population based studies in our laboratory, yields poor overlap between the two mapping approaches, while both local-eQTL studies show highly concordant results. Specifically, local-eQTL studies show ~60% overlap between themselves, while only 15-20% of local-eQTLs are identified as cis by ASE, and less than 50% of ASE genes are recovered in local-eQTL studies. Utilizing recently published ENCODE data, we also find that ASE genes show significant bias for SNPs prevalence in DNase I hypersensitive sites that is ASE direction specific. We suggest a new approach to analysis of allele specific expression that is more sensitive and accurate than the commonly used fisher or chi-square statistics. Our analysis indicates that technical differences between the cis and local-eQTL approaches, such as differences in genomic background or sex specificity, account for relatively small fraction of the discrepancy. Therefore, we suggest that the differences between two eQTL mapping approaches may facilitate sorting of SNP-eQTL interactions into true cis and trans, and that a considerable portion of local-eQTL may actually represent trans interactions. 4 samples - male and female, BxD and DxB adipose of pooled RNA (3 animals per pool) were analyzed with high coverage RNAseq data.
2014-06-05 | E-GEOD-58239 | biostudies-arrayexpress
Project description:In this study we use RNAseq to explore allele specific expression (ASE) in adipose tissue of male and female F1 mice, produced from reciprocal crosses of C57BL/6J and DBA/2J strains. Comparison of the identified cis-eQTLs, to local-eQTLs, that were obtained from adipose tissue expression in two previous population based studies in our laboratory, yields poor overlap between the two mapping approaches, while both local-eQTL studies show highly concordant results. Specifically, local-eQTL studies show ~60% overlap between themselves, while only 15-20% of local-eQTLs are identified as cis by ASE, and less than 50% of ASE genes are recovered in local-eQTL studies. Utilizing recently published ENCODE data, we also find that ASE genes show significant bias for SNPs prevalence in DNase I hypersensitive sites that is ASE direction specific. We suggest a new approach to analysis of allele specific expression that is more sensitive and accurate than the commonly used fisher or chi-square statistics. Our analysis indicates that technical differences between the cis and local-eQTL approaches, such as differences in genomic background or sex specificity, account for relatively small fraction of the discrepancy. Therefore, we suggest that the differences between two eQTL mapping approaches may facilitate sorting of SNP-eQTL interactions into true cis and trans, and that a considerable portion of local-eQTL may actually represent trans interactions.
2014-06-05 | GSE58239 | GEO
Project description:Genotyping 323 Europeans in order to perform cis-eQTL analysis in 9 tissue cell types. Identification of regulatory modules across genes and tissues on the basis of correlated SNPs in expression associated patterns. Integration of cis-eQTLs regulatory modules with known 200 IBD loci.
2018-04-28 | E-MTAB-6666 | biostudies-arrayexpress