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Association of leucocyte telomere length with frailty: a large-scale cross-sectional analysis in UK Biobank

By Vasiliki Bountziouka, Christopher P Nelson, Veryan Codd, Qingning Wang, Crispin Musicha, Elias Allara, Stephen Kaptoge, Emanuele Di Angelantonio, Adam S Butterworth, John R Thompson, Elizabeth M Curtis, Angela M Wood, John N Danesh, Nicholas C Harvey, Cyrus Cooper, Nilesh J. Samani

Posted 13 Jun 2021
medRxiv DOI: 10.1101/2021.06.11.21258736

Background: Leucocyte telomere length (LTL), a potential marker of biological age, has been associated with risk of many diseases. We investigated whether LTL is associated with risk of frailty, a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Methods: In a cross-sectional analysis, we studied 441,781 UK Biobank participants (aged 40-70 years), with complete data on LTL and frailty indicators. We defined frailty as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past two weeks. We evaluated association of LTL with frailty using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, multimorbidity) multinomial and ordinal regression models. We used Mendelian randomisation (MR), using 131 genetic variants associated with LTL, to assess if the association of LTL with frailty was causal. Findings: Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years), more likely to be female (61%), and had shorter LTL (-0.13SD vs 0.03SD) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (OR=1.03 (95%CI: 1.02; 1.04) per year of older chronological age; 1.10 (1.08; 1.11) per SD shorter LTL). Within each age group (40-49, 50-59, 60-69 years) the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant. Interpretation: Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.

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