Genetics and Epigenetics of Cardiovascular Disease

National Human Genome Research Institute

Investigators

Linked publications, trials & patents

Abstract

Two studies nested in GENE-FORECAST have been initiated: - Sodium Intervention Trial (SIT) The objective of this study is to implement a sodium intervention investigation to assess the effect of increased dietary sodium intake on changes in blood pressure, vascular function, microbiome, whole blood epigenome, whole blood and urine transcriptome as outcome measures. The study design will include a double-blind, cross-over treatment/placebo trial among 40 former African Americans GENEFORECAST participants with normal blood pressure and will last 7weeks. It is hypothesized that exposure to increased dietary sodium will affect blood pressure, whole blood epigenome, whole blood and urine transcriptome, vascular function, microbiome and blood pressure. - COVID-19 The objective is to conduct a prospective natural history study of Coronavirus disease 2019 (COVID-19) among a community-based cohort of African Americans enrolled in GENE-FORECAST for whom we have comprehensive psychosocial, clinical, and genetic data collected at baseline. Participants will be invited to take part in a 20-minute computer-assisted telephone interview (CATI) on exposures, attitudes and circumstances during the COVID-19 pandemic and to undergo a clinic visit for a physical exam, vascular function tests and biospecimen collection. We will identify social, clinical and genetic risk factors for COVID-19 and examine the interplay between social determinants of health and personal risk profiles to better understand the disparate burden of COVID-19 in the African American community. It is hypothesized that exposure to the SARS-CoV-2 virus and the development of COVID-19 will be associated with social and neighborhood factors, and that SARSCoV-2 infection will adversely affect vascular function. - Data Infrastructure Given the multiple ongoing omics assays (Multi-ethnic array genotyping, whole-genome sequencing, mRNA and microRNA sequencing, methylation sequencing, metabolome, microbiome and telomere assay), CDS has developed robust computer infrastructure and sequencing pipelines to support analyses through actively computing, imputing, and simulating genomic and phenotypic models developed by dimensionality reduction techniques to gain useful insights from large genomic data sets. This computational infrastructure has now been transferred to a cloud-based platform (BioData Catalyst) to benefit from storage and computing elasticity in the cloud and integrate standardized pipelines and algorithms developed by the scientific community for cloud computing. - Analyses CDS has also developed an analytical framework which uses both conventional statistical and Machine Learning techniques to integrates those various data sources and provide a more comprehensive picture of the traits of interest and the interplay between the underlying determinants. The framework makes use of data already collected or projected to be collected by CDS as part of MH-GRID, GENE-FORECAST. This analytical framework is being used in the current projects listed below. (1) MicroRNA study of Metabolic Healthy Obesity (2) Social Disadvantage, Gene Expression and Depressive Symptoms in African American from MH-GRID (3) Exome-wide association study (EWAS) of 8 cardiometabolic traits (4) Developing a transcriptome-informed polygenic risk score of reduced kidney function in African American with hypertension (5) Developing a transcriptome-informed polygenic risk score of hypertension in African American (6) Whole-blood Transcriptome study of Coronary Artery Calcium (7) Transcriptome signature of sodium intake in and links to cardiovascular traits (8) Transcriptome and proteome study of Coronary Artery Calcium (CAC)