Date on Master's Thesis/Doctoral Dissertation

12-2023

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Epidemiology and Population Health

Degree Program

Public Health Sciences with a specialization in Epidemiology, PhD

Committee Chair

Taylor, Kira

Committee Member

Lange, Leslie

Committee Member

Baumgartner, Baumgartner

Committee Member

DuPré, Natalie

Committee Member

Mitra, Riten

Author's Keywords

genetic epidemiology; epidemiology; genetic risk score; GRS; HT; CKD

Abstract

Hypertension (HT) and chronic kidney diseases (CKD) are complex conditions, disproportionally prevalent among African Americans (AA) and are influenced by multiple genetic as well as environmental factors. Genetic risk scores (GRS) enable the analysis of the combined effects of multiple single nucleotide polymorphisms (SNPs). This study investigates the association of blood pressure (BP) and CKD GRS with BP, hypertension (HT) and CKD; early-onset HT and CKD; and investigates interactions of the GRSs with environmental measures in AA. We observed a significant association between the BP-GRS with HT, SBP and DBP. The odds of HT for one standard deviation (s.d.) increase in the SBP-GRS and DBP-GRS increased by 59% [OR (95%CI): 1.59 (1.43, 1.77)] and 40% [OR (95%CI): 1.40 (1.26, 1.55)] respectively, adjusted for age, sex and genetic ancestry. The odds of CKD for one s.d. increase in the CKDGRS increased by 85% [OR (95%CI): 1.85 (1.64, 2.09)]. Notably, CKD-GRS was also significantly associated with HT and DBP but not with SBP. For a one s.d. increase in the CKDGRS, the odds of HT increased by 10% (OR (95%CI): 1.10 (1.01, 1.20)) and DBP increased by 0.37 mmHg (95% CI: 0.01, 0.73). Analyses using the early-onset outcomes (HT and CKD) were similar to those above, but slightly attenuated. These results were not meaningfully modified by salt, smoking, alcohol, or sex in this analysis, though there was a modest suggestion of interaction between the risk scores and BMI. vi This study adds evidence towards utilizing GRS in clinical settings to identify high risk AA individuals and target preventative measures such as more frequent screening and support for positive lifestyle changes. Additionally, our study suggests that HT may be a consequence rather than a cause of CKD, which implies that measures taken to control hypertension alone may not be sufficient for preventing CKD. The use of an AA population to generate a GRS for CKD is suggested as a next step; in addition, identifying variants specific for early-onset HT and CKD could result in a more powerful prediction score for these conditions and help elucidate their etiology.

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