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ASSOCIATION OF LEUKOCYTE TELOMERE LENGTH AND GENETIC BIOMARKERS OF LEUKOCYTE TELOMERE LENGTH WITH PERCEIVED PHYSICAL AND MENTAL FATIGABILITY

Katz, Ryan (2021) ASSOCIATION OF LEUKOCYTE TELOMERE LENGTH AND GENETIC BIOMARKERS OF LEUKOCYTE TELOMERE LENGTH WITH PERCEIVED PHYSICAL AND MENTAL FATIGABILITY. Master Essay, University of Pittsburgh.

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Abstract

Background: Fatigue is a common complaint in older adults, and perceived fatigability is associated with disability and mortality. In the Long Life Family Study (LLFS), perceived physical and mental fatigability are heritable, although genetic biomarkers related to fatigability have not been identified. Genome wide linkage and association analysis has identified multiple loci associated with leukocyte telomere length (LTL), a potential marker of cellular aging.
Objective: The primary objective of this analysis was to determine whether LTL predicts physical and mental fatigability. A secondary objective was to investigate the relationship between genetic biomarkers associated with LTL and fatigability.
Methods: In LLFS, LTL was assayed at baseline (2006-2009) and perceived physical and mental fatigability were measured at Visit 2 (2014-2017) using the validated Pittsburgh Fatigability Scale (PFS, 0-50, higher scores indicating greater fatigability). We performed multivariate linear regression with continuous PFS outcomes and logistic regression with previously established cut-points (≥15 for physical and ≥13 for mental fatigability) to determine whether LTL and SNPs associated with LTL were predictive of fatigability. All models accounted for family structure and were adjusted for field center.
Results: Shorter LTL predicted higher PFS Physical scores (β=2.7, p<0.0001) and greater physical fatigability (OR=1.50, 95%CI [1.22, 1.85], p=0.0001). After adjusting for sex, chronic conditions, and lifestyle factors, the relationship remained significant for continuous scores (β=1.7, p<0.0001) and trended non-significant for the dichotomous outcome (OR=1.38, 95%CI [1.10, 1.73], p=0.057). Shorter LTL predicted higher PFS Mental scores (β=1.7, p=0.0004) and greater mental fatigability (OR=1.35, 95%CI [1.03, 1.78], p=0.032). After full adjustment, the relationship was borderline for continuous scores (β=0.8, p=0.055) and non-significant for greater mental fatigability (OR=1.11, 95%CI [1.21, 1.48], p=0.50). None of the SNPs investigated were associated with fatigability.
Conclusion: LTL predicted physical and mental fatigability, and was more closely related to physical fatigability. Genetic markers examined were not related to fatigability. Additional research to characterize the genetic basis of fatigability and its role in the disability pathway will allow interventions that preserve function in older adults, which will be increasingly important for public health as older adults make up a growing proportion of the overall population.


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Details

Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Katz, Ryanryan.katz@pitt.edurdk32
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairGlynn, Nancyepidnwg@pitt.edu
Committee MemberKammerer, Candacecmk3@pitt.edu
Committee MemberZmuda, Josephjmz64@pitt.edu
Date: 10 February 2021
Date Type: Completion
Submission Date: 10 December 2020
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 46
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Uncontrolled Keywords: Fatigue, aging, heritability, cohort study, SNPs
Date Deposited: 10 Feb 2021 16:05
Last Modified: 10 Feb 2021 16:05
URI: http://d-scholarship.pitt.edu/id/eprint/40075

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  • ASSOCIATION OF LEUKOCYTE TELOMERE LENGTH AND GENETIC BIOMARKERS OF LEUKOCYTE TELOMERE LENGTH WITH PERCEIVED PHYSICAL AND MENTAL FATIGABILITY. (deposited 10 Feb 2021 16:05) [Currently Displayed]

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