Genetics of high serum triglycerides and related metabolic traits in Mexicans
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PROVIDER: PRJNA202274 | ENA |
REPOSITORIES: ENA
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Project description:Genetics of high serum triglycerides and related metabolic traits in Mexicans
| PRJNA202275 | ENA
Project description:Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10-6) and blood triglycerides (P = 1.39x10-5). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10-4) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21, Pcombined = 5.20x10-9). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer.
2016-11-06 | GSE65319 | GEO
Project description:Heritable epigenetic factors can contribute to complex disease etiology. In this study we examine, on a global scale, the contribution of DNA methylation to complex traits that are precursors to heart disease, diabetes and osteoporosis. We profiled DNA methylation patterns in the liver using bisulfite sequencing in 90 mouse inbred strains, genome-wide expression levels, proteomics, metabolomics and sixty-eight clinical traits, and performed epigenome-wide association studies (EWAS). We found associations with numerous clinical traits including bone mineral density, plasma cholesterol, insulin resistance, gene expression, protein and metabolite levels. A large proportion of associations were unique to EWAS and were not identified using GWAS. Methylation levels were regulated by genetics largely in cis, but we also found evidence of trans regulation, and we demonstrate that genetic variation in the methionine synthase reductase gene Mtrr affects methylation of hundreds of CpGs throughout the genome. Our results indicate that natural variation in methylation levels contributes to the etiology of complex clinical traits. Reduced representation bisulfite sequencing in mouse strains using liver genomic DNA
2015-04-02 | E-GEOD-67507 | biostudies-arrayexpress
Project description:Heritable epigenetic factors can contribute to complex disease etiology. In this study we examine, on a global scale, the contribution of DNA methylation to complex traits that are precursors to heart disease, diabetes and osteoporosis. We profiled DNA methylation patterns in the liver using bisulfite sequencing in 90 mouse inbred strains, genome-wide expression levels, proteomics, metabolomics and sixty-eight clinical traits, and performed epigenome-wide association studies (EWAS). We found associations with numerous clinical traits including bone mineral density, plasma cholesterol, insulin resistance, gene expression, protein and metabolite levels. A large proportion of associations were unique to EWAS and were not identified using GWAS. Methylation levels were regulated by genetics largely in cis, but we also found evidence of trans regulation, and we demonstrate that genetic variation in the methionine synthase reductase gene Mtrr affects methylation of hundreds of CpGs throughout the genome. Our results indicate that natural variation in methylation levels contributes to the etiology of complex clinical traits.
2015-04-02 | GSE67507 | GEO
Project description:The spontaneously hypertensive rat (SHR) is the most widely used model of essential hypertension and is predisposed to left ventricular hypertrophy, myocardial fibrosis, and metabolic disturbances. Recently, a quantitative trait locus (QTL) influencing blood pressure, left ventricular mass and heart interstitial fibrosis was genetically isolated within 788 kb on chromosome 8 segment of SHR-PD5 congenic strain that contains only 7 genes, including mutant Plzf (promyelocytic leukemia zinc finger) gene. To identify Plzf as a quantitative trait gene, we targeted Plzf in the SHR using the TALEN technique and obtained SHR line harboring mutant Plzf gene with a premature stop codon at position of amino acid 58. The Plzf mutant allele is semi-lethal since approximately 95% of newborn homozygous animals die perinatally due to multiple developmental abnormalities. Heterozygous rats were grossly normal and were used for metabolic and hemodynamic analyses. SHR-Plzf+/- heterozygotes versus SHR wild type controls exhibited reduced body weight and relative weight of epididymal fat, lower serum and liver triglycerides and cholesterol and better glucose tolerance. In addition, SHR-Plzf+/- rats exhibited significantly increased sensitivity of adipose and muscle tissue to insulin action when compared to wild type controls. Blood pressure was comparable in SHR versus SHR-Plzf+/-, however, there was significant amelioration of cardiomyocyte hypertrophy and cardiac fibrosis in SHR-Plzf+/- rats. Gene expression profiles in the liver and expression of selected genes in the heart revealed differentially expressed genes playing a role in metabolic pathways, PPAR signaling, and cell cycle regulation. These results provide evidence for an important role of Plzf in regulation of metabolic and cardiac traits in the rat and suggest a cross-talk between cell cycle regulators, metabolism, cardiac hypertrophy and fibrosis.
2016-07-03 | E-MTAB-3831 | biostudies-arrayexpress
Project description:Peanut is one of the most important cash crops with high quality oil, high protein content, and many other nutritional elements, and grown globally. Cultivated peanut (Arachis hypogaea L.) is allotetraploid with a narrow genetic base, and its genetics and molecular mechanisms controlling the agronomic traits are poorly understood. The array SNP data was used for revaling of key candidate loci and genes associated with important agronomic traits in peanut
2022-02-22 | GSE197103 | GEO
Project description:OBJECTIVE: Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome-related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs). RESEARCH DESIGN AND METHODS: We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model. RESULTS: Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin. CONCLUSIONS: The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR.
| S-EPMC2845050 | biostudies-literature
Project description:This study examines the best way to teach genetics to family medicine residents. First year family medicine residents at the University of Toronto will be taught basic clinical genetics as well as a specific disease in genetics via 3 different educational methods. All participants will undergo an oral examination and written knowledge test 3 months after this education. Results between groups will be compared, and the best way to teach genetics to residents determined.
| 2030694 | ecrin-mdr-crc
Project description:Tissue-specific gene expression and gene regulation lead to a better understanding of tissue-specific physiology and pathophysiology. We analyzed the transcriptome and genetic regulatory profiles of two distinct gastric sites, corpus and antrum, to identify tissue-specific gene expression and its regulation. The transcriptome data from corpus and antral mucosa highlights the heterogeneity of gene expression in the stomach. We identified enriched pathways revealing distinct and common physiological processes in gastric corpus and antrum. Physiological differences are mostly related to digestion and epithelial protection. Furthermore, we found an enrichment of the single nucleotide polymorphism (SNP)-based heritability of metabolic, obesity-related, and cardiovascular traits and diseases by considering corpus- and antrum-specifically expressed genes. In particular, we could prioritize gastric-specific candidate genes for multiple metabolic traits, like NQO1 which is involved in glucose metabolism, MUC1 which contributes to purine and protein metabolism or RAB27B being a regulator of weight and body composition.
2024-02-23 | GSE242339 | GEO
Project description:The genetics of messenger RNA expression has been extensively studied in humans and other organisms, but little is known about genetic factors contributing to microRNA (miRNA) expression. We examined natural variation of miRNA expression in adipose tissue in a population of 200 men who have been carefully characterized for metabolic syndrome phenotypes as part of the METSIM study. We genotyped the subjects using high-density SNP microarrays and quantified the mRNA abundance using genome-wide expression arrays and miRNA abundance using next generation sequencing. We reliably quantified 356 miRNA species that were expressed in human adipose tissue, a limited number of which made up most of the expressed miRNAs. We mapped the miRNA abundance as an expression quantitative trait and determined cis regulation of expression for 9 of the miRNAs and of the processing of one miRNA (miR-28). The degree of genetic variation of miRNA expression was substantially less than that of mRNAs. For the majority of the miRNAs, genetic regulation of expression was independent of the host mRNA transcript expression. We also showed that for 108 miRNAs, mapped reads displayed widespread variation from the canonical sequence. We found a total of 24 miRNAs to be significantly associated with metabolic syndrome traits. We suggest a regulatory role for miR-204-5p which was predicted to inhibit ACACB, a key fatty acid oxidation enzyme that has been shown to play a role in regulating body fat and insulin resistance in adipose tissue. miRNA expression profiling of adipose tissue isolated from 200 humans
2013-04-01 | E-GEOD-45159 | biostudies-arrayexpress