Kibbutzim Family study
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ABSTRACT:
PROVIDER: EGAD00010001551 | EGA |
REPOSITORIES: EGA
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Project description:The Kibbutzim Family Study (KFS) was established in 1992 to investigate the environmental and genetic determinants of cardiometabolic risk factors and their change over time. The participants belong to large families living in close-knit communities, called “Kibbutzim”, in Northern Israel. The Kibbutz has been a communal settlement, which has created a relatively homogeneous environment for its members. Kibbutz members are mostly of Ashkenazi Jewish ancestry, with the remaining members belonging to other Jewish subgroups. Participants were recruited in two phases from six Kibbutzim. In the first recruitment phase of the study (1992–1993) 500 individuals from 80 extended families (range 2 to 43) were examined. During the second phase (1999–2000), all participants from the first phase were invited for repeat examinations (80% response rate) and additional new participants were recruited, giving a total of 922 individuals from 150 extended families (range 2 to 55). Families were invited to participate if they consisted of at least four individuals who (i) lived in the Kibbutz, (ii) spanned at least two generations, and (iii) were at least 15 years old. Families were retained if at least two family members consented to participate in the study. Overall, 1033 participants were recruited; 111 were examined only in the first phase, 533 only in the second phase, and 389 were included in both. 901 individuals were successfully genotyped using Illumina HumanCoreExome BeadChip.
| EGAS00001002782 | EGA
Project description:Primary outcome(s): Prediction of malignant phenotype of colorectal cancer by serum and exosomal CEA family and detection of circulating tumor cells.
| 2629030 | ecrin-mdr-crc
Project description:Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTL) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTL have been identified in a limited set of human tissues. Here we mapped caQTL in human liver tissue in 20 liver samples and identified 3,123 caQTL. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTL. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTL and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTL contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci.
2021-05-01 | GSE164870 | GEO
Project description:Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTL) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTL have been identified in a limited set of human tissues. Here we mapped caQTL in human liver tissue in 20 liver samples and identified 3,123 caQTL. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTL. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTL and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTL contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci.
2021-05-01 | GSE164938 | GEO
Project description:Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTL) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTL have been identified in a limited set of human tissues. Here we mapped caQTL in human liver tissue in 20 liver samples and identified 3,123 caQTL. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTL. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTL and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTL contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci.
2021-05-01 | GSE164876 | GEO
Project description:Aims: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial disease that constitutes several distinct phenotypes, including a common cardiometabolic phenotype with obesity and type 2 diabetes mellitus. Treatment options for HFpEF are limited, and development of novel therapeutics is hindered by the paucity of suitable preclinical HFpEF models that recapitulate the complexity of human HFpEF. Metabolic drugs, like Glucagon Like Peptide Receptor Agonist (GLP-1RA) and Sodium Glucose Transporter 2 inhibitors (SGLT2i), have emerged as promising drugs to restore metabolic perturbations and may have value in the treatment of the cardiometabolic HFpEF phenotype. We aimed to develop a multifactorial HFpEF mouse model that closely resembles the cardiometabolic HFpEF phenotype, and evaluated the GLP-1 RA liraglutide and a SGLT2i dapagliflozin. Methods&Results: Aged (18-22 months old) female C57BL/6J mice were fed a standardized chow (CTRL) or high fat diet (HFD) for 12 weeks. After 8 weeks HFD, Angiotensin-II (ANGII), was administered for 4 weeks via osmotic mini-pumps. HFD+ANGII resulted in a cardiometabolic HFpEF phenotype, including obesity, impaired glucose handling and metabolic dysregulation with inflammation. The multiple-hit resulted in typical clinical HFpEF features, including cardiac hypertrophy and fibrosis with preserved fractional shortening but with impaired myocardial deformation, atrial enlargement lung congestion, and elevated blood pressures. Treatment with liraglutide attenuated the cardiometabolic dysregulation and improved cardiac function, with reduced cardiac hypertrophy, less myocardial fibrosis, and attenuation of atrial weight, natriuretic peptide levels, and lung congestion. Dapagliflozin treatment improved glucose handling, but had mild effects on the HFpEF phenotype. Conclusions: We developed a mouse model that recapitulates the human HFpEF disease, providing a novel opportunity to study disease pathogenesis and development of enhanced therapeutic approaches. We furthermore show that attenuation of cardiometabolic dysregulation may represent a novel therapeutic target for treatment of HFpEF.
2020-09-16 | GSE153923 | GEO
Project description:Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor of the liver, characterized by high malignancy, poor prognosis, and lack of effective treatment.Solute carrier family 12 member 5 (SLC12A5) is frequently overexpressed in many tumors and is involved in the development and progression of several human cancers. Here, we aimed to investigate the expression and biological function of SLC12A5 in ICC.
2023-02-01 | GSE220911 | GEO