NHLBI TOPMed: GOLDN Epigenetic Determinants of Lipid Response to Dietary Fat and Fenofibrate

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 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. The diet intervention followed the protocol of Patsch et al. (1992). 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. Comprehensive phenotypic and pedigree data for GOLDN study participants are available through dbGaP phs000741.]]>
TOPMed Whole Genome Sequencing Methods: Freeze 8TOPMed Whole Genome Sequencing Methods: Freeze 9To participate in the GOLDN study, participants were required to be identified through families previously screened in the NHLBI FHS Minnesota or Utah centers. Because FHS was conducted exclusively in participants of Caucasian descent, the GOLDN population is entirely white, and this was scientifically acceptable when originally funded because (a) the source cohort was all of Caucasian descent and (b) PROGENI as a program had representation from other ethnic groups. For GOLDN, eligible family members were 18 years of age or older, had fasting triglycerides < 1500 mg/dL, were in a family with at least two members in a sibship, had normal liver function tests (i.e., aspartate transaminase and alanine transaminase tests within normal range), and creatinine values ≤ 2.0. Anyone with a history of liver, kidney, pancreas, gall bladder disease or malabsorption was excluded, as were pregnant women or women of childbearing potential not using an acceptable form of contraception, or anyone requiring insulin to treat diabetes. Individuals using hypolipidemic drugs were asked to consult with their physician and were taken off medications at least four weeks prior to the study after informed consent for drug withdrawal was obtained. Participants in the current study provided written informed consent to DNA sharing options that allowed future research to be conducted from stored specimens.]]>