Inflammation Genomics and Atherosclerosis - Ancillary to CARDIA
Condition: Cardiovascular Diseases; Atherosclerosis; Coronary Arteriosclerosis; Inflammation; Heart Diseases; Thrombosis
MeSH terms: Cardiovascular Diseases; Heart Diseases; Thrombosis; Atherosclerosis; Arteriosclerosis; Coronary Artery Disease; Myocardial Ischemia; Inflammation
Study type: Observational

Summary: 
      To examine the associations of common variation in inflammation/thrombosis genes with
      intermediate quantitative phenotypes and subclinical coronary atherosclerosis in the Coronary
      Artery Risk Factor Development in Young Adults (CARDIA) Study, a large, bi-racial cohort
      study.
    

Detailed description: 
      BACKGROUND:

      Atherosclerosis is a major determinant of coronary heart disease and is determined by the
      interplay of genetic and environmental risk factors. Although atherosclerosis tends to
      aggregate in families, it does not exhibit classical Mendelian segregation. Thus, the genes
      that determine an individual's risk of atherosclerosis likely involve multiple sites within
      genes and interactions between genes, all of which define a genetic risk that is modified by
      the host environment.

      DESIGN NARRATIVE:

      The genetic epidemiology study examines the associations of common variation in
      inflammation/thrombosis genes with intermediate quantitative phenotypes and subclinical
      coronary atherosclerosis in the Coronary Artery Risk Factor Development in Young Adults
      (CARDIA) Study, a large, bi-racial cohort study. The set of 25 candidate genes involve
      pathways (cytokines, chemokines, and their receptors; cellular adhesion molecules; and,
      coagulation proteins) and include several receptor-ligand pairs. Using cladistic analysis and
      the resources of the Program in Genomic Applications (PGA), the investigators will identify a
      limited set of single nucleotide polymorphisms (range 3-10 SNPs per gene) that characterize
      common haplotypes in these candidate genes within persons of African descent and European
      descent. DNA from the CARDIA Year 10 examination (n = 3,950 subjects) will be genotyped for
      the selected variants that characterize the common haplotypes. Data on the presence of common
      variants and haplotypes will be incorporated into the CARDIA Study database. Levels of two
      important intermediate phenotypes, fibrinogen and C-reactive protein (CRP) were previously
      determined. Non-invasive assessment of coronary atherosclerosis, defined as the presence of
      coronary artery calcification (CAC), was obtained on CARDIA participants at the Year 15 exam.
      Analyses will be stratified by race/ethnicity and focus on the associations of the common
      haplotypes with fibrinogen, CRP, and CAC measured in early adult life. Secondarily, the
      investigators will explore possible gene-gene and gene-environment interactions. The proposed
      multi-disciplinary collaboration should enhance the sensitivity and specificity of efforts to
      assess the associations of common variation in sets of inflammation/thrombosis candidate
      genes and cardiovascular risk in young adults.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Same as eligibility criteria