Genetic analysis of carotid artery intima-media thickness (IMT)

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Genetic factors strongly contribute to the development of atherosclerosis and its major clinical manifestations, myocardial infarction and stroke. To identify previously unknown genes that are involved in the development of atherosclerosis we propose to study common carotid artery intima-media thickness (IMT) as an intermediate phenotype. In preparation of the present project we recruited 156 nuclear families, consisting of an index patient with manifest atherosclerosis, his/her partner and their common offspring. Access to a large population-based sample of independent subjects derived from the Carotid Atherosclerosis Progression Study (CAPS) was established.The primary goal of this project is to identify one or more chromosomal loci with significant linkage to common carotid artery IMT. To this end, we plan to perform a genome-wide linkage scan in the available family sample. In parallel, we will enlarge the family sample to 300 nuclear families. The second goal is to evaluate the association of genetic variants of candidate genes in the most promising chromosomal region with IMT. These studies will be done in the CAPS sample.