The overall goal of this project is to identify genes that contribute to cardiovascular disease (CVD) byinvestigating subclinical atherosclerosis within diabetes-affected families in the Diabetes Heart Study (DHS), apopulation at an increased risk of developing CVD. Identification of the genes that contribute to subclinicalatherosclerosis phenotypes such as coronary artery and carotid artery calcified plaque (CorCP and CarCP),abdominal aortic calcified plaque (AACP) and carotid artery intima-media wall thickness (IMT), will further theunderstanding of the pathogenesis of cardiovascular diseases. We have conducted genome scans for each ofthese vascular calcification phenotypes using affected sibling pairs from the DHS. We detected a linkage peak forCarCP on chromosome 16p13.13-p13.3 with a LOD score of 3.82 in European American diabetics. Our goal isto use fine mapping followed by positional cloning to identify variants in genes that contribute to CarCPsusceptibility in the European American diabetic population. We will further analyze the existing data by includingadditional covariate adjustments, and exploring pleiotropy and gene by environment interactions. The region oflinkage will be refined by genotyping additional single nucleotide polymorphisms (SNPs), and the construction of adense SNP map within the refined region will aid in the identification of haplotypes associated with the CarCPphenotype. A focused evaluation of candidate genes encompassed by these haplotypes will aid in theidentification of specific alleles responsible for CarCP susceptibility.PHS416-
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