Mapping of disease-associated expression polymorphisms in primary peripheral blood CD4+ lymphocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22324 | GEO | 2010/06/14
SECONDARY ACCESSION(S): PRJNA127537
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of expression quantitative trait loci (eQTLs) using RNA derived from freshly harvested peripheral blood CD4+ lymphocytes from 200 asthmatics collected in clinical settings. RNA was obtained from peripheral blood CD4+ lymphocytes at four study centers. Peripheral blood (17 cc) was collected into BD Vacutainer CPT tubes (BD Diagnostics, Franklin Lakes, New Jersey) and placed on ice. Samples were centrifuged within 1 hour of collection for 20 minutes at 1700RCF, followed by mononuclear cell layer isolation and suspension in 10 ml of PBS. We isolated CD4+ lymphocytes using anti-CD4+ microbeads by column separation (Miltenyi Biotec, Auburn, CA) using 20 µl anti-CD4+ Micro beads per 106 total cells
2010-06-23 | E-GEOD-22324 | biostudies-arrayexpress
Project description: Not available
| S-EPMC2972694 | biostudies-literature
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:Research into the genetic influences of impulsivity and reward motivated behavior relies heavily on outbred animal populations, including Heterogeneous Stock (HS) rats, for the genetic diversity necessary to identify genotype-trait associations. Many such associations have been detected, but it is not always clear which gene or other feature near the identified genomic location is functionally responsible for the association. Since these traits are in part mediated by gene expression, mapping the associations between genotype and gene expression in these animals will enable the discovery and deeper understanding of these trait associations. We therefore obtained genotypes and RNA-Seq gene expression for five brain regions from 88 HS rats and mapped expression quantitative trait loci (eQTLs) for each region. We identified cis-eQTLs in over 3,000 genes per brain region and validated their effect sizes using allele specific expression. This resource will enable new discoveries of the genetic influences of complex behavioral traits.
2021-04-23 | GSE173140 | GEO
Project description:Research into the genetic influences of impulsivity and reward motivated behavior relies heavily on outbred animal populations, including Heterogeneous Stock (HS) rats, for the genetic diversity necessary to identify genotype-trait associations. Many such associations have been detected, but it is not always clear which gene or other feature near the identified genomic location is functionally responsible for the association. Since these traits are in part mediated by gene expression, mapping the associations between genotype and gene expression in these animals will enable the discovery and deeper understanding of these trait associations. We therefore obtained genotypes and RNA-Seq gene expression for five brain regions from 88 HS rats and mapped expression quantitative trait loci (eQTLs) for each region. We identified cis-eQTLs in over 3,000 genes per brain region and validated their effect sizes using allele specific expression. This resource will enable new discoveries of the genetic influences of complex behavioral traits.
2021-04-23 | GSE173139 | GEO
Project description:Research into the genetic influences of impulsivity and reward motivated behavior relies heavily on outbred animal populations, including Heterogeneous Stock (HS) rats, for the genetic diversity necessary to identify genotype-trait associations. Many such associations have been detected, but it is not always clear which gene or other feature near the identified genomic location is functionally responsible for the association. Since these traits are in part mediated by gene expression, mapping the associations between genotype and gene expression in these animals will enable the discovery and deeper understanding of these trait associations. We therefore obtained genotypes and RNA-Seq gene expression for five brain regions from 88 HS rats and mapped expression quantitative trait loci (eQTLs) for each region. We identified cis-eQTLs in over 3,000 genes per brain region and validated their effect sizes using allele specific expression. This resource will enable new discoveries of the genetic influences of complex behavioral traits.
2021-04-23 | GSE173138 | GEO
Project description:Research into the genetic influences of impulsivity and reward motivated behavior relies heavily on outbred animal populations, including Heterogeneous Stock (HS) rats, for the genetic diversity necessary to identify genotype-trait associations. Many such associations have been detected, but it is not always clear which gene or other feature near the identified genomic location is functionally responsible for the association. Since these traits are in part mediated by gene expression, mapping the associations between genotype and gene expression in these animals will enable the discovery and deeper understanding of these trait associations. We therefore obtained genotypes and RNA-Seq gene expression for five brain regions from 88 HS rats and mapped expression quantitative trait loci (eQTLs) for each region. We identified cis-eQTLs in over 3,000 genes per brain region and validated their effect sizes using allele specific expression. This resource will enable new discoveries of the genetic influences of complex behavioral traits.
2021-04-23 | GSE173137 | GEO
Project description:The functional interpretation of GWAS remains challenging due to the cell-type dependent influences of genetic variants. Here, we generated comprehensive maps of expression quantitative trait loci (eQTL) for 659 microdissected human kidney samples and identified cell-type eQTLs by mapping interactions between cell type abundance and genotype. By partitioning heritability using stratified LD-score regression to integrate GWAS with scRNA-seq and snATAC-seq data, we prioritized proximal tubules in kidney function and endothelial cells and distal tubule segments in blood pressure pathogenesis. Bayesian colocalization analysis nominated more than 200 genes for kidney function and hypertension. Our study clarifies the mechanism of commonly used antihypertensive and renal protective drugs and identifies drug repurposing opportunities for kidney disease.
2021-05-10 | GSE172008 | GEO
Project description:Research into the genetic influences of impulsivity and reward motivated behavior relies heavily on outbred animal populations, including Heterogeneous Stock (HS) rats, for the genetic diversity necessary to identify genotype-trait associations. Many such associations have been detected, but it is not always clear which gene or other feature near the identified genomic location is functionally responsible for the association. Since these traits are in part mediated by gene expression, mapping the associations between genotype and gene expression in these animals will enable the discovery and deeper understanding of these trait associations. We therefore obtained genotypes and RNA-Seq gene expression for five brain regions from 88 HS rats and mapped expression quantitative trait loci (eQTLs) for each region. We identified cis-eQTLs in over 3,000 genes per brain region and validated their effect sizes using allele specific expression. This resource will enable new discoveries of the genetic influences of complex behavioral traits.
2021-04-23 | GSE173136 | GEO