Paediatrics (RCH) - Theses
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ItemSleep, telomere length and cardiorespiratory phenotypes in a population-based cohort of children and mid-life adults( 2021)Background: Telomeres are biomarkers for health and aging. In older adults, short telomeres are associated with poorer cardiovascular and respiratory (cardiorespiratory) health, but little corresponding data is available at earlier ages. This is important given that the pathogenesis of such diseases begins in childhood. Cumulative modifiable exposures, such as sleep, also influence telomere length; however, there is a lack of studies in adults, and even fewer in childhood. This is critical, given that life-long health patterns are formed in childhood, making it an important period for intervention. Shortened telomeres may, therefore, partly mediate the relationship between sleep and cardiorespiratory phenotypes. Aims: In a national population-based cohort of children and their parents, my thesis aimed to (I) describe the epidemiology of telomere length and parent-child telomere length concordance; examine associations of (II) telomere length with cardiovascular phenotypes, (III) telomere length with respiratory phenotypes and (IV) sleep with telomere length; and (V) examine whether telomere length mediates the relationship between sleep and cardiorespiratory health. Methodology: Design and participants–Children aged 11–12 years and their parents in the Child Health CheckPoint study, a physical health assessment in 2015 nested in the Longitudinal Study of Australian Children. Measures–Sleep characteristics (sleep duration, timing, variability, efficiency), cardiovascular phenotypes (carotid intima-media thickness [carotid IMT], carotid elasticity, carotid-femoral pulse wave velocity [carotid-femoral PWV]), respiratory phenotypes (forced expired volume in 1 second [FEV1], forced vital capacity [FVC], FEV1/FVC ratio and maximum mid-expiratory flow [MMEF25-75]), relative telomere length (T/S ratio). Analysis–Distributions using means and standard deviations (SD) and density plots. Parent-child concordance using the Pearson correlations. Multivariable linear/logistic regression quantified associations of telomere length with cardiorespiratory phenotypes, and sleep characteristics with telomere length. Results: Aim I–Children had longer telomeres than adults (n=1206, T/S ratio 1.09 vs. n=1343, 0.81 units), but also showed a wider spread to higher values, and did not differ by sex at either age. Parent-child telomere length concordance was greater in father-child than mother-child pairs, which was stronger in younger parents. Aim II–In adults, longer telomeres were associated with greater carotid elasticity, but not for carotid IMT or carotid-femoral PWV, or any measure in children. Aim III–In adults, longer telomeres were associated with higher FEV1/FVC and MMEF25-75 z-scores, but not for FEV1 or FVC, or any measure in children. Aim IV–Little evidence of association between sleep characteristics and telomere length at either age. Conclusion: At 11–12 years, both parents contribute to child telomere length and concordance may be stronger when the parent-child age gap is smaller. Associations between worse vascular function (e.g. lower carotid elasticity) and airflow limitation (lower FEV1/FVC and MMEF25-75) with shortened telomeres emerged by mid-life adulthood, and thus might imply that cardiorespiratory risk trajectories are at least partially established after 11–12 years. Regarding Aim V, telomere length appears to have a limited role in mediating the known link between sleep and cardiorespiratory health. The strength of the association could also be due to chance and hence requires replication, and ideally utilising longitudinal investigations with repeated sampling.