Date of Award

Summer 2025

Language

English

Embargo Period

7-24-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Epidemiology and Biostatistics

Program

Epidemiology

First Advisor

Mark Kuniholm

Committee Members

Elizabeth Vásquez, Kathy Chou

Keywords

polygenic risk score, grip strength, HIV, MACS, WIHS, frailty, aging, genetic risk score

Subject Categories

Epidemiology | Genetics and Genomics

Abstract

Background: Adequate hand function among older adults is necessary for the successful completion of activities of daily living and can affect whether an older adult is able to live independently. Current research highlights grip strength, the strength people have in their hands, as a robust predictor of morbidity and mortality, and explores the decline in grip strength over time. A person’s family history and genes (DNA) affect how much grip strength they have. Previous studies have identified genes that affect grip strength, mainly in European ancestry populations. In this study, we examined whether these genetic elements predict grip strength in a multiracial United States (US) cohort study of people living with and without human immunodeficiency virus (HIV), and if this association is influenced by HIV status.

Methods: We used demographic, clinical and genetic data from the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS). In both MACS and WIHS participants, grip strength was measured using a Jamar® hydraulic handheld dynamometer, with 3 trials at each visit. The maximum of the 3 trials was used as the grip strength phenotype variable. Using grip strength influencing genetic variants, specifically Single Nucleotide Polymorphisms (SNPs), identified in previous studies, we created polygenic risk scores (PRS) that combined information from multiple SNPs into a single metric. We conducted cross-sectional analyses using a single grip strength measurement and repeated measures analysis using multiple grip strength measurements in each participant to study their association with the PRS. We also tested for associations of individual genes with grip strength, and any differences by HIV status. All analyses were conducted separately in men and women due to differences in sociodemographic characteristics beyond sex (e.g., race, ethnicity, education, income) and protocol differences with grip strength measurement frequency (semiannual in MACS, annual in WIHS).

Results: We observed significant associations between PRS of grip strength and continuous grip strength in MACS men older than 50 years of age in the combined group of HIV + and HIV- participants, when adjusted for 10 principal components of ancestry (PCs) and HIV in both cross-sectional (β =0.09, standard error (se) =0.03, p-value = 0.01) and in repeated measures (β =0.06, se =0.02, p-value = 0.03) analyses. We also observed significant associations in seronegative men older than 50 years in cross-sectional analysis (β =0.12, se =0.05, p-value = 0.01) and in HIV-positive men older than 50 years in repeated measures analysis (β =0.08, se =0.03, p-value = 0.04). No effect modification by HIV status was seen in the MACS cohort. There were no significant associations observed in the WIHS cohort in any analysis.

Conclusion: PRS of grip strength with SNPs derived from European ancestry populations were associated with continuous grip strength in men older than 50 years from the MACS cohort, regardless of the HIV status. This study demonstrates that PRS of grip strength developed for the general population could predict grip strength in people with HIV. PRS of grip strength may help identify low grip strength and support the design of interventions to promote healthy aging among people with or at risk for HIV.

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This work is licensed under the University at Albany Standard Author Agreement.

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Available for download on Friday, July 24, 2026

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