Understanding the Genetic and Hereditary Basis of Atherosclerosis

• To estimate the association between common single nucleotide polymorphisms (SNPs) in the human genome and extent of subclinical atherosclerosis among subjects in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) cohort (N=2,876). [ Time Frame: Entire project period. ] [ Designated as safety issue: No ]
  
• To estimate the association between potential atherosclerosis SNPs identified in the PDAY cohort and extent of subclinical atherosclerosis among subjects in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (N=6,577). [ Time Frame: Entire project period ] [ Designated as safety issue: No ]
  
• To define the haplotypic structure of the genome in the regions of SNPs that are associated with atherosclerosis in PDAY and MESA and to perform additional genotyping necessary for haplotype association studies using both the PDAY and MESA cohorts. [ Time Frame: Entire project period. ] [ Designated as safety issue: No ]
  
• To disseminate the identity, location, primer sets and allele frequency of the atherosclerosis associated SNPs in PDAY, and those confirmed in MESA, in order to facilitate additional replication and functional studies of the most promising SNPs. [ Time Frame: Entire project period. ] [ Designated as safety issue: No ]
  

Atherosclerosis is a condition in which deposits of fat, cholesterol, and other substances build up along the inner walls of arteries; these deposits are known as plaque. As plaque builds up, it increases the risk of blood clots, heart attack, and stroke. Research has shown that the risk of developing atherosclerosis can be influenced by heredity. However, researchers have been unable to identify the specific genes associated with this risk. Single nucleotide polymorphisms (SNPs) are small genetic variations that can occur within an individual's DNA. In this study, researchers will analyze the DNA of many individuals for differences in SNP patterns. The goal of the study is to determine which SNP patterns are associated with the development of atherosclerosis. The data from this study may lead to new strategies for early identification of high risk individuals who may benefit from aggressive treatment to prevent the development of atherosclerosis.

This study will not recruit any new participants. DNA will be collected and analyzed from participants in two existing studies—the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study and the Multi-Ethnic Study of Atherosclerosis (MESA). DNA from the PDAY participants will be obtained from liver samples gathered during an autopsy following the participants' deaths; DNA from the MESA participants will be obtained from blood collected during routine study visits. There will be no additional study visits for participants, and all DNA samples and study information will be kept confidential. Genetic testing will be performed to determine the association between SNPs and subclinical atherosclerosis, which is a form of the condition prior to the onset of symptoms. The study will evaluate specific variations in SNPs and subclinical disease among different ethnic groups, which may help to explain why certain ethnic groups have higher rates of atherosclerosis. The study will also examine the association between SNPs and other indicators of subclinical and clinical atherosclerosis, including the thickness of arteries, heart calcium levels, and blood pressure levels.