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Genetic Epidemiology of Hypertension in Populations: Applications of Modified Methods

Shetty, Priya Bhatia
http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Epidemiology and Biostatistics.
Objective: Modified methods of analysis were applied in three studies of African-Americans to identify variants associated with blood pressure and to address missing heritability in genetic studies of hypertension. Methods: Three genetic epidemiology studies were conducted in African-American subjects in the National Heart, Lung and Blood Institute’s Family Blood Pressure Program. First, a candidate gene association study using gene scores was conducted in genomic regions that previously showed admixture association evidence for blood pressure and other cardiovascular traits. Second, admixture mapping analyses were conducted on the 22 autosomal chromosomes for blood pressure and lipids, followed by fine-mapping analyses of the suggestive admixture regions in families. Third, admixture mapping analyses were conducted for blood pressure in subjects treated with at least 2 anti-hypertensive medications, and the regions suggesting admixture evidence were followed up with fine-mapping analyses in families to identify variants associated with apparent treatment-resistant hypertension. Stratified analyses were conducted by number of drugs for phenotypes showing significant association results in all subjects. Results: In the first study, CXADR and F2RL1 were associated with blood pressure and body-mass-index, respectively. Analysis of local ancestry suggested that other associated SNPs were present in these regions. In the second study, the admixture mapping analyses identified seven regions associated with blood pressure and lipids. In the fine-mapping analyses, 11 SNPs in 8 independent loci were identified for associations with lipids. In the third study, admixture regions on chromosomes 3 and 5 were identified for association with blood pressure in all treated subjects and in subjects taking two anti-hypertensive drugs, respectively. The regions included variants that were previously identified in a large blood pressure GWAS, and the results suggested that the variants were associated with treatment response, rather than blood pressure, in African-Americans. Conclusions: A number of novel and known genomic and genetic variants were identified for blood pressure and other cardiovascular phenotypes. The methods of analysis were modified to incorporate gene scores, two-stage study designs and fine-mapping association analyses in families, and these adaptations were key in addressing some of the missing heritability in the genetics of hypertension and other cardiovascular traits.
Xiaofeng Zhu, PhD (Advisor)
Robert Elston, PhD (Committee Member)
Jing Li, PhD (Committee Member)
Nathan Morris, PhD (Committee Member)
150 p.
Epidemiology; Genetics
genetic epidemiology; admixture mapping analysis; candidate gene analysis; African-Americans; blood pressure; cardiovascular disease

Recommended Citations

Citations

  • Shetty, P. B. (2014). Genetic Epidemiology of Hypertension in Populations: Applications of Modified Methods [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333

    APA Style (7th edition)

  • Shetty, Priya. Genetic Epidemiology of Hypertension in Populations: Applications of Modified Methods. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333.

    MLA Style (8th edition)

  • Shetty, Priya. "Genetic Epidemiology of Hypertension in Populations: Applications of Modified Methods." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333

    Chicago Manual of Style (17th edition)

case1385562333
836
© 2013, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.