Carotid artery intima-media thickness (IMT) and distensibility represent structural and functional subclinical carotid disease, respectively. They can be measured by ultrasound, and can be used as intermediate phenotypes for clinical stroke/cardiovascular events. Studies have shown that increased carotid IMT or decreased distensibility are independent risk factors for myocardial infarction and stroke. Furthermore, family studies reported that appreciable heritability in both intermediate phenotypes, which indicates strong genetic influence on the development of carotid thickness and stiffness. These findings warrant the endeavor to map genetic markers to these two phenotypes. The main goal of this research is to study the genetic polymorphisms associated with carotid IMT and distensibility in the three race/ethnic groups (whites, blacks and Hispanics) from the Northern Manhattan Study (NOMAS) cohort. The strengths of the current application include: 1) both phenotypic data have been measured in a large cohort (n about 1500); 2) the cohort includes three race/ethnic groups, which provides an invaluable data source to compare genetic effect across three major race/ethnic groups in the USA; 3) new technologies in molecular genetics, comparative genomics and statistical genetics will be employed in our studies, and 4) the NOMAS Family Study has been supported by the NIH, which will allow us to evaluate the genetic effect on IMT and distensibility by linkage analysis. Therefore, the results from the current application can be validated from a different study design and analytic approach. The development of IMT and distensibility may involve lipid metabolism, molecule adhesion, endothelial function, smooth muscle proliferation, inflammation and structural integrity of the vessel wall. We propose to investigate several potential genes involved in these processes. Primary Aims: 1. To determine the association between carotid IMT, distensibility and polymorphisms of 16 candidate genes in the three race/ethnic groups from Northern Manhattan. 2. To create marker haplotypes and perform haplotype analysis using in-house newly developed programs. 3. To explore a newly developed statistical method to evaluate the overall genetic effects from all candidate genes to obtain """"""""whole-pathway"""""""" effects.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Gwinn, Katrina
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Della-Morte, David; Gardener, Hannah; Dong, Chuanhui et al. (2018) Association Between Carotid Artery Function and Structure in the Northern Manhattan Study. Front Neurol 9:246
Boillot, Adrien; Demmer, Ryan T; Mallat, Ziad et al. (2015) Periodontal microbiota and phospholipases: the Oral Infections and Vascular Disease Epidemiology Study (INVEST). Atherosclerosis 242:418-23
Dong, Chuanhui; Della-Morte, David; Beecham, Ashley et al. (2015) Genetic variants in LEKR1 and GALNT10 modulate sex-difference in carotid intima-media thickness: a genome-wide interaction study. Atherosclerosis 240:462-7
Desvarieux, Moïse; Demmer, Ryan T; Jacobs, David R et al. (2013) Changes in clinical and microbiological periodontal profiles relate to progression of carotid intima-media thickness: the Oral Infections and Vascular Disease Epidemiology study. J Am Heart Assoc 2:e000254
Rundek, Tatjana; Blanton, Susan H; Bartels, Susanne et al. (2013) Traditional risk factors are not major contributors to the variance in carotid intima-media thickness. Stroke 44:2101-8
Della-Morte, David; Beecham, Ashley; Dong, Chuanhui et al. (2012) Association between variations in coagulation system genes and carotid plaque. J Neurol Sci 323:93-8
Dong, Chuanhui; Beecham, Ashley; Wang, Liyong et al. (2012) Follow-up association study of linkage regions reveals multiple candidate genes for carotid plaque in Dominicans. Atherosclerosis 223:177-83
Wang, Liyong; Beecham, Ashley; Zhuo, Degen et al. (2012) Fine mapping study reveals novel candidate genes for carotid intima-media thickness in Dominican Republican families. Circ Cardiovasc Genet 5:234-41
Della-Morte, David; Beecham, Ashley; Rundek, Tatjana et al. (2011) A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes. BMC Med Genet 12:100
Dong, Chuanhui; Della-Morte, David; Wang, Liyong et al. (2011) Association of the sirtuin and mitochondrial uncoupling protein genes with carotid plaque. PLoS One 6:e27157

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