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Genetic Epidemiology of Subclinical Cardiovascular Disease and Osteoporosis Indices in African Ancestry Families

Kuipers, Allison Lindsay (2011) Genetic Epidemiology of Subclinical Cardiovascular Disease and Osteoporosis Indices in African Ancestry Families. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    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.


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    Item Type: University of Pittsburgh ETD
    ETD Committee:
    ETD Committee TypeCommittee MemberEmail
    Committee ChairZmuda, Joesph Mzmudaj@edc.pitt.edu
    Committee MemberKammerer, Candace Mcmk3@pitt.edu
    Committee MemberBunker, Clareann Hbunkerc@pitt.edu
    Committee MemberMiljkovic, Ivamiljkovici@edc.pitt.edu
    Committee MemberSutton-Tyrrell, Kimtyrrell@edc.pitt.edu
    Title: Genetic Epidemiology of Subclinical Cardiovascular Disease and Osteoporosis Indices in African Ancestry Families
    Status: Unpublished
    Abstract: 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.
    Date: 29 June 2011
    Date Type: Completion
    Defense Date: 31 March 2011
    Approval Date: 29 June 2011
    Submission Date: 21 March 2011
    Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
    Patent pending: No
    Institution: University of Pittsburgh
    Thesis Type: Doctoral Dissertation
    Refereed: Yes
    Degree: PhD - Doctor of Philosophy
    URN: etd-03212011-122313
    Uncontrolled Keywords: Afro-Caribbean; arterial diameter; bone mineral density; genome-wide linkage analysis; heritability; intima-media thickness; pulse pressure; pulse-wave velocity
    Schools and Programs: Graduate School of Public Health > Epidemiology
    Date Deposited: 10 Nov 2011 14:32
    Last Modified: 07 Mar 2012 14:23
    Other ID: http://etd.library.pitt.edu/ETD/available/etd-03212011-122313/, etd-03212011-122313

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