Project description:<p>The Cholesterol and Pharmacogenetics Study was a 6-week open label, non-randomized study of 40mg/day simvastatin treatment in 944 African-American and Caucasian men and women. Plasma lipid and lipoprotein were measured on two occasions prior to treatment and at 4 and 6 weeks of treatment. The study was designed to test for genetic associations to baseline measurements and changes in response to simvastatin treatment.</p> <p>Whole genome genotyping was performed on 592 Caucasians CAP study participants in two stages. In Stage 1, 304 were genotyped for 314,621 SNPs to tag for common genomic variation. In Stage 2, 290 subjects were genotyped, which included 280 subjects genotyped for 620,901 SNPs. Two samples were excluded due to gender discrepancies.</p>
Project description:<p>The Cholesterol and Pharmacogenetics Study was a 6-week open label, non-randomized study of 40mg/day simvastatin treatment in 335 African-American and 609 Caucasian (944 total) men and women. Plasma lipids and lipoproteins were measured on two occasions prior to treatment and at 4 and 6 weeks of treatment. The study was designed to test for genetic associations with baseline measurements and changes in response to simvastatin treatment.</p> <p>Whole genome genotyping was performed on 592 Caucasian CAP study participants in two stages. In Stage 1, 304 were genotyped for 314,621 SNPs to tag for common genomic variation. In Stage 2, 290 participants were genotyped, including 280 who were genotyped for 620,901 SNPs. Two samples were excluded due to gender discrepancies.</p> <p>PolyA-selected strand-specific RNA-seq libraries were generated from lymphoblastoid cell lines (LCLs) derived from 104 Caucasian and 53 African American CAP participants. The LCLs were exposed to sham buffer (control) or 2 uM activated simvastatin for 24 hours, producing a total of 314 100/101 bp paired end RNA-seq libraries sequenced on Illumina HiSeq 2000 machines.</p>
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.
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/
Project description:To investigate the effect of Progranulin on neutrophils phagocytosis and killing of Candida albicans, we designed RNA-Seq analysis of wild-type and PGRN-/- neutrophils challenged with Candida albicans in vitro at one time point.