An immune response network associated with blood lipid levels
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ABSTRACT:
PROVIDER: EGAS00000000086 | EGA |
REPOSITORIES: EGA
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An immune response network associated with blood lipid levels.
Inouye Michael M Silander Kaisa K Hamalainen Eija E Salomaa Veikko V Harald Kennet K Jousilahti Pekka P Männistö Satu S Eriksson Johan G JG Saarela Janna J Ripatti Samuli S Perola Markus M van Ommen Gert-Jan B GJ Taskinen Marja-Riitta MR Palotie Aarno A Dermitzakis Emmanouil T ET Peltonen Leena L
PLoS genetics 20100909 9
While recent scans for genetic variation associated with human disease have been immensely successful in uncovering large numbers of loci, far fewer studies have focused on the underlying pathways of disease pathogenesis. Many loci which are associated with disease and complex phenotypes map to non-coding, regulatory regions of the genome, indicating that modulation of gene transcription plays a key role. Thus, this study generated genome-wide profiles of both genetic and transcriptional variati ...[more]
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Project description:While recent scans for genetic variation associated with human disease have been immensely successful in uncovering large numbers of loci, far fewer studies have focused on the underlying pathways of disease pathogenesis. Many loci which are associated with disease and complex phenotypes map to non-coding, regulatory regions of the genome, indicating that modulation of gene transcription plays a key role. Thus, this study generated genome-wide profiles of both genetic and transcriptional variation from the total blood extracts of over 500 randomly-selected, unrelated individuals. Using measurements of blood lipids, key players in the progression of atherosclerosis, three levels of biological information are integrated in order to investigate the interactions between circulating leukocytes and proximal lipid compounds. Pair-wise correlations between gene expression and lipid concentration indicate a prominent role for basophil granulocytes and mast cells, cell types central to powerful allergic and inflammatory responses. Network analysis of gene co-expression showed that the top associations function as part of a single, previously unknown gene module, the Lipid Leukocyte (LL) module. This module replicated in T cells from an independent cohort while also displaying potential tissue specificity. Further, genetic variation driving LL module expression included the single nucleotide polymorphism (SNP) most strongly associated with serum immunoglobulin E (IgE) levels, a key antibody in allergy. Structural Equation Modeling (SEM) indicated that LL module is at least partially reactive to blood lipid levels. Taken together, this study uncovers a gene network linking blood lipids and circulating cell types and offers insight into the hypothesis that the inflammatory response plays a prominent role in metabolism and the potential control of atherogenesis.
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Project description:We performed genotyping of Neuroblastoma Primary tumors using Illumina HumanHap 550 - v1,v3,v3duo and 610 Quad genotyping beadchips.
2011-09-15 | GSE19385 | GEO
Project description:Genetic heterogeneity is an important feature of solid tumors, however it is often assumed that most cancer cell lines are genetically homogeneous. A disparity in genetic complexity between cell lines and the disease they model could result in problems such as in vitro preclinical experiments overstating the effectiveness of putative therapeutics. We therefore derived clonal sublines by single cell cloning of in house derived early passage melanoma cell lines (LM-MEL-series), and compared their genomes to each other and the parental cell line using Illumina 610-Quad SNP arrays.
2013-09-08 | E-MTAB-1753 | biostudies-arrayexpress
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2019-09-10 | GSE121225 | GEO
Project description:BackgroundEpigenetic mechanisms might be involved in the regulation of interindividual lipid level variability and thus may contribute to the cardiovascular risk profile. The aim of this study was to investigate the association between genome-wide DNA methylation and blood lipid levels high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Observed DNA methylation changes were also further analyzed to examine their relationship with previous hospitalized myocardial infarction.Methods and resultsGenome-wide DNA methylation patterns were determined in whole blood samples of 1776 subjects of the Cooperative Health Research in the Region of Augsburg F4 cohort using the Infinium HumanMethylation450 BeadChip (Illumina). Ten novel lipid-related CpG sites annotated to various genes including ABCG1, MIR33B/SREBF1, and TNIP1 were identified. CpG cg06500161, located in ABCG1, was associated in opposite directions with both high-density lipoprotein cholesterol (β coefficient=-0.049; P=8.26E-17) and triglyceride levels (β=0.070; P=1.21E-27). Eight associations were confirmed by replication in the Cooperative Health Research in the Region of Augsburg F3 study (n=499) and in the Invecchiare in Chianti, Aging in the Chianti Area study (n=472). Associations between triglyceride levels and SREBF1 and ABCG1 were also found in adipose tissue of the Multiple Tissue Human Expression Resource cohort (n=634). Expression analysis revealed an association between ABCG1 methylation and lipid levels that might be partly mediated by ABCG1 expression. DNA methylation of ABCG1 might also play a role in previous hospitalized myocardial infarction (odds ratio, 1.15; 95% confidence interval=1.06-1.25).ConclusionsEpigenetic modifications of the newly identified loci might regulate disturbed blood lipid levels and thus contribute to the development of complex lipid-related diseases.
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Project description:Objectives. The present study aimed to evaluate the effect of CD40 and CXCR4 genes polymorphisms on CAD susceptibility and the blood lipid levels and history of cardiovascular risk factors in a Chinese Han population. Materials and Methods. A total of 583 unrelated patients with CAD and 540 controls were recruited. Two tag SNPs (rs4239702 and rs1535045) at the CD40 locus and one tag SNP (rs2228014) at the CXCR4 locus were genotyped using the SEQUENOM Mass-ARRAY system. Results. After adjusting the risk factors, the frequency of rs1535045-T allele was also higher in patients than controls. Haplotype analysis showed that the rs4239702(C)-rs1535045(T) haplotype was associated with CAD. People with rs4239702-TT genotype had higher blood lipid levels in case group while it was not in the control group. History of cardiovascular risk factors showed no association for the three SNPs in case group and control group. Conclusions. rs1535045 in CD40 gene is likely to be associated with CAD in the Chinese Han population. rs4239702(C)-rs1535045(T) haplotype was associated with CAD. Only in CAD patients, the blood lipid level of patients with rs4239702-TT genotype was higher than other patients. CXCR4 gene may not relate to CAD.
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Project description:Variation in relative abundance of gut bacteria correlates with lipid profiles in healthy adults
| PRJEB43699 | ENA
Project description:Hispanic/Latino populations possess a complex genetic structure that reflects recent admixture among and potentially ancient substructure within Native American, European, and West African source populations. Here, we quantify genome-wide patterns of SNP and haplotype variation among 100 individuals with ancestry from Ecuador, Colombia, Puerto Rico, and the Dominican Republic genotyped using Illumina technology. To investigate variations of continental ancestry between different Hispanic/Latino groups (using self-reported country-specific identification of individual, both parents, and all four grandparents) and within them from healthy controls represented in the New York Health Project Biorepository. Genotyped on the Illumina 610-Quad, which is identical to HumanHap550-v3 SNPs plus an additional ~60,000 SNPs for CNV, no CNV data is provided or was analyzed.
2010-04-07 | E-GEOD-21248 | biostudies-arrayexpress
Project description:BACKGROUND:In low and middle-income countries (LMIC), the total and LDL cholesterol and triglyceride levels of residents of urban areas are reported to be higher than those of rural areas. This may be due to differences in lifestyle behaviors between residents of urban areas and rural areas in LMIC. In this study, our aims were to (1) examine whether or not LDL cholesterol, total/HDL ratios and triglyceride levels of individuals in densely populated areas are higher than those of individuals living in less-densely populated areas in a high-income country (HIC) and (2) investigate the potential mediating roles of physical activity and sedentary behavior. METHODS:We used cross-sectional data from 2547 Dutch blood donors that participated in Donor InSight-III. Linear regression was used to analyze the association between population density and LDL cholesterol, total/HDL cholesterol ratio and HDL cholesterol. The mediating roles of moderate-to-vigorous physical activity (MVPA) and sedentary behavior were investigated in a subsample (n?=?740) for which objectively measured MVPA/sedentary behavior data was available. Multiple mediation with linear regression analyses were performed and the product-of-coefficients method was used to calculate direct and indirect effects. RESULTS:Mean LDL cholesterol and median total cholesterol/HDL cholesterol ratio and triglyceride levels were 2.89, 3.43 and 1.29 mmol/L, respectively. Population density was not associated with LDL cholesterol [? 0.00 (- 0.01; 0.01)], log transformed total/HDL cholesterol ratio [? 1.00 (1.00; 1.00)] and triglyceride levels [? 1.00 (0.99; 1.00)]. No statistically significant direct or indirect effects were found. CONCLUSION:Contrary to previous findings in LMIC, no evidence was found that population density is associated with blood lipid levels in blood donors in the Netherlands or that MVPA and sedentary behavior mediate this association. This may be the result of socioeconomic differences and, in part, may be due to the good health of the study population and the relatively high population density in the Netherlands. Also, compared to LMIC, differences in physical activity levels in more versus less populated areas may be less pronounced in HIC.
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