Cardiovascular disease (CVD) is a major public health concern, especially in African ancestry populations, which have greater risk compared with Caucasians. Subclinical CVD measures provide information on the health of the vasculature and are predictive of future risk of clinical events. Vascular health indices have been associated with lower bone mineral density (BMD) and osteoporosis suggesting a potential common etiology. Intima-media thickness (IMT) and arterial diameter (adventitial diameter [AD] and lumen diameter [LD]) are subclinical CVD measures obtained by carotid ultrasound, whereas pulse pressure (PP) and pulse-wave velocity (PWV) are subclinical measures of arterial stiffness. The genetic influence on these subclinical CVD measures and in the link between CVD and osteoporosis has not been well defined in African ancestry populations. Therefore, we have estimated genetic heritability, genetic correlation of CVD and osteoporosis related traits, and performed univariate and bivariate genome-wide linkage analysis of these traits in 7 large, multigenerational families of African ancestry from the Caribbean island of Tobago. A total of 461 individuals aged ¡Ý18 years were included in these analyses from probands and families who were recruited without regard to their health status. After removing the effects of covariates, subclinical CVD traits were all heritable and there was significant phenotypic and genetic correlation between CVD and osteoporosis related traits. The most promising evidence of linkage was detected for AD-BMD trait-pairs on chromosome 14 (max LOD=5.2) in bivariate analysis and for AD and LD on chromosome 11 (max LOD=4.1) in univariate analysis. The linkage regions contain several genes known to be involved in cardiovascular disease including the ApoA1/C3/A4/A5 gene cluster, IL18, BMP4, and ESR2. Further studies of these regions may reveal novel insight into the genetic regulation of subclinical CVD and osteoporosis. These findings have public health significance because determining the genetic regulation of chronic disease may aid in risk prediction and, ultimately, minimize health disparities in African ancestry populations.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-03212011-122313 |
| Date | 29 June 2011 |
| Creators | Kuipers, Allison Lindsay |
| Contributors | Kim Sutton-Tyrrell, Candace M Kammerer, Iva Miljkovic, Clareann H Bunker, Joesph M Zmuda |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-03212011-122313/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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