Novel Genetic Factors for Subclinical Carotid Atherosclerosis

The overall goal for this study was to determine the genetic factors associated with extreme phenotypes of subclinical atherosclerosis (protective and deleterious). Study participants were selected from the Northern Manhattan Study (NOMAS), a population based cohort study investigating stroke and stroke risk factors in Northern Manhattan. Cases and controls were individuals at the extreme ends of the distribution for carotid intima-media thickness and carotid plaque, with cases defined as individuals with subclinical atherosclerosis that could not be explained by traditional vascular risk factors (USAth) and controls defined as individuals with unexplained protection against atherosclerosis (UPAth).]]> Individuals in the extreme top and bottom 20% (Hispanics) and 30% (Blacks and Whites) of the residual distribution for cIMT and carotid plaque were included in this study. Residual cIMT and carotid plaque distributions were calculated after adjusting for age, sex, pack-years of smoking, systolic blood pressure, diabetes, LDL: HDL ratio, LDL level, homocysteine levels, high school completion, lipid lowering medication, and white blood cell counts.]]> Name of Grant: Novel Factors for Unexplained Phenotypes of Subclinical Carotid Atheroscerosis Agency number: NIH 5R01NS065114-01 PIs: Tatjana Rundek, MD, PhD and Susan H. Blanton, PhD Dates: Specific Aims: 1. Identify a subset of individuals with Unexplained Subclinical Atherosclerosis (USAth) or Unexplained Protection against Atherosclerosis (UPAth) using 2-D carotid ultrasound imaging of carotid plaque burden, 2. Identify genes that are associated with USAth and UPAth by performing a genome wide association study (GWAS) (Discovery Sample), 3. Validate the GWAS findings in the remaining NOMAS sample, an independent sample of a family-based cohort, and in the SNP Health Association Resource (SHARe) Project (Validation Samples) and 4. Perform follow-up studies of the 2 most significant SNPs/CNVs to identify the underlying causal variant]]>