GOLDN: Genetics of Lipid Lowering Drugs and Diet Network Study
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PROVIDER: PRJNA546418 | ENA |
REPOSITORIES: ENA
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Project description:GOLDN: Genetics of Lipid Lowering Drugs and Diet Network Study
| PRJNA546419 | ENA
Project description:Genetics of Lipid Lowering Drugs and Diet Network Study (GOLDN): GWAS
| PRJNA246011 | ENA
Project description:<p>The GOLDN study was initiated to assess how genetic factors interact with environmental (diet and drug) interventions to influence blood levels of triglycerides and other atherogenic lipid species and inflammation markers (registered at clinicaltrials.gov, number <a href="https://clinicaltrials.gov/ct2/show/NCT00083369" target="_blank">NCT00083369</a>). The study recruited Caucasian participants primarily from three-generational pedigrees from two NHLBI Family Heart Study (FHS) field centers (Minneapolis, MN and Salt Lake City, UT). Only families with at least two siblings were recruited and only participants who did not take lipid-lowering agents (pharmaceuticals or nutraceuticals) for at least 4 weeks prior to the initial visit were included. The diet intervention followed the protocol of Patsch et al. (<a href="https://www.ncbi.nlm.nih.gov/pubmed/1420093" target="_blank">1992</a>). The whipping cream (83% fat) meal had 700 Calories/m2 body surface area (2.93 mJ/m2 body surface area): 3% of calories were derived from protein (instant nonfat dry milk) and 14% from carbohydrate (sugar). The ratio of polyunsaturated to saturated fat was 0.06 and the cholesterol content of the average meal was 240 mg. The mixture was blended with ice and flavorings. Blood samples were drawn immediately before (fasting) and at 3.5 and 6 hours after consuming the high-fat meal. The diet intervention was administered at baseline as well as after a 3-week treatment with 160 mg micronized fenofibrate. Participants were given the option to complete one or both (diet and drug) interventions. Of all participants, 1079 had phenotypic data and provided appropriate consent, and underwent whole genome sequencing through the Trans-Omics for Precision Medicine (TOPMed) program.</p> <p>Comprehensive phenotypic and pedigree data for GOLDN study participants are available through dbGaP <a href="./study.cgi?study_id=phs000741">phs000741</a>.</p>
| phs001359 | dbGaP
Project description:Thromboembolic events secondary to rupture or erosion of advanced atherosclerotic lesions are the leading cause of death in the world. The most common and effective means to reduce these major adverse cardiovascular events (MACE), including myocardial infarction (MI) and stroke, is aggressive lipid lowering via a combination of drugs and dietary modifications. However, little is known regarding the effects of reducing dietary lipids on the composition and stability of advanced atherosclerotic lesions, the mechanisms that regulate these processes, and what therapeutic approaches might augment the benefits of lipid lowering.
2024-05-06 | GSE264253 | GEO
Project description:Genetics of Lipid Lowering Drugs and Diet Network Study (GOLDN): GWAS
| PRJNA246012 | ENA
Project description:<p>The GOLDN study was initiated to assess how genetic factors interact with environmental (diet and drug) interventions to influence blood levels of triglycerides and other atherogenic lipid species and inflammation markers (registered at <a href="http://clinicaltrials.gov/ct2/show/NCT00083369">clinicaltrails.gov</a>, number NCT00083369). The study recruited Caucasian participants primarily from three-generational pedigrees from two NHLBI Family Heart Study (FHS) field centers (Minneapolis, MN and Salt Lake City, UT). Only families with at least two siblings were recruited and only participants who did not take lipid-lowering agents (pharmaceuticals or nutraceuticals) for at least 4 weeks prior to the initial visit were included. A total of 1048 GOLDN participants were included in the diet intervention. The diet intervention followed the protocol of Patsch et al. (<a href="http://www.ncbi.nlm.nih.gov/pubmed/1420093">1992</a>). The whipping cream (83% fat) meal had 700 Calories/m2 body surface area (2.93 MJ/m2 body surface area): 3% of calories were derived from protein (instant nonfat dry milk) and 14% from carbohydrate (sugar). The ratio of polyunsaturated to saturated fat was 0.06 and the cholesterol content of the average meal was 240 mg. The mixture was blended with ice and flavorings. Blood samples were drawn immediately before (fasting) and at 3.5 and 6 hours after consuming the high-fat meal. For the GOLDN lipidomics study, sterols and fatty acids were measured from stored plasma (-80 degrees Celsius) collected at fasting and 3.5 hours after the diet intervention using TrueMass Panels from Lipomics (West Sacramento, CA). A total of 11 sterols were quantified in nmols/gram of sample including total cholesterol, 7-dehydrocholesterol, desmosterol, lanosterol, lathasterol, cholestanol, coprostanol, beta-sitosterol, campesterol, stigmasterol, and 7alpha-hydroxycholesterol. A total of 35 fatty acids were quantified in nmols/gram of sample inlcuding myristic acid (14:0); pentadecanoic acid (15:0); palmitic acid (16:0); stearic acid (18:0); arachidic acid (20:0); behenic acid (22:0); lignoceric acid (24:0); myristoleic acid (14:1n5); palmitoleic acid (16:1n7); palmitelaidic acid (t16:1n7); oleic acid (18:1n9); elaidic acid (t18:1n9); vaccenic acid (18:1n7); linoleic acid (18:2n6); gamma-linolenic acid (18:3n6); alpha-linolenic acid (18:3n3); stearidonic acid (18:4n3); eicosenoic acid (20:1n9); eicosadienoic acid (20:2n6); mead acid (20:3n9); di-homo-gamma-linolenic acid (20:3n6); arachidonic acid (20:4n6); eicsoatetraenoic acid (20:4n3); eicosapentaenoic acid (20:5n3); erucic acid (22:1n9); docosadienoic acid (22:2n6); adrenic acid (22:4n6); docosapentaenoic acid (22:5n6); docosapentaenoic acid (22:5n3); docosahexaenoic acid (22:6n3); nervonic acid (24:1n9); and plasmalogen derivatives of 16:0, 18:0, 18:1n9, and 18:1n7.</p>
| phs000741 | dbGaP
Project description:Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10-8/132 = 4 × 10-10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p < 8.0 × 10-7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p < 3.3 × 10-3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal.
| S-EPMC8617762 | biostudies-literature
Project description:IL-1β inhibition partially negates the beneficial effects of diet-induced lipid lowering
| PRJNA1101548 | ENA
Project description:Immune checkpoint inhibitor (ICI) therapies in cancer accelerate atherosclerosis progression. Here, we have charted the landscape of immune checkpoint gene expression and defined the network of disease-relevant interactions with single-cell resolution. We found that signaling through PD-1 and CTLA4 is driven by a population of dendritic cells enriched for FSCN1 that can be derived from peripheral blood cells following anti-PD-1 or -CTLA4 treatment ex vivo. Type 2 diabetes dampened plaque PD-1 and CTLA4 signaling, showing that cardiometabolic comorbidities elicit unique responses to ICIs. Lipid-lowering therapy equalized the intensity and direction of immune checkpoint interactions in human blood, while atherosclerotic mice subjected to a lipid-lowering diet displayed both increased co-inhibitory signaling and a downregulation of inflammatory transcriptional programs in plaques. Our findings underscore the potential of lipid-lowering therapies in stabilizing immune checkpoint interactions and reducing plaque inflammation, offering new insights on atherosclerosis and cardiovascular risks in cancer patients undergoing ICI treatments.
2024-12-18 | GSE246317 | GEO
Project description:Immune checkpoint inhibitor (ICI) therapies in cancer accelerate atherosclerosis progression. Here, we have charted the landscape of immune checkpoint gene expression and defined the network of disease-relevant interactions with single-cell resolution. We found that signaling through PD-1 and CTLA4 is driven by a population of dendritic cells enriched for FSCN1 that can be derived from peripheral blood cells following anti-PD-1 or -CTLA4 treatment ex vivo. Type 2 diabetes dampened plaque PD-1 and CTLA4 signaling, showing that cardiometabolic comorbidities elicit unique responses to ICIs. Lipid-lowering therapy equalized the intensity and direction of immune checkpoint interactions in human blood, while atherosclerotic mice subjected to a lipid-lowering diet displayed both increased co-inhibitory signaling and a downregulation of inflammatory transcriptional programs in plaques. Our findings underscore the potential of lipid-lowering therapies in stabilizing immune checkpoint interactions and reducing plaque inflammation, offering new insights on atherosclerosis and cardiovascular risks in cancer patients undergoing ICI treatments.
2024-12-18 | GSE246315 | GEO