SEARCHCOHORTcardiology, epidemiology

cohort·cardiology, epidemiology, observational study, biomedical research·PMC10828293

Associations of measured and genetically predicted leukocyte telomere length with vascular phenotypes: a population-based study

GeroScience · 5 authors, 3 centres

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TL;DR

This cross-sectional population study examined associations between leukocyte telomere length (LTL) and various vascular phenotypes. It found that measured LTL and the difference between measured and genetically predicted LTL (ΔLTL) were associated with microvascular function and cardiac index, while genetically predicted LTL was only associated with cardiac index.

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Genetically predicted LTL was only associated with cardiac index. An epigenome-wide association study linked genes whose methylation was associated with ΔLTL to vascular endothelial growth factor pathways.

STUDY TYPE

cohort

SPECIALTY

cardiology

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AI pipeline

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ORIGINAL PAPER

PMC10828293

Associations of measured and genetically predicted leukocyte telomere length with vascular phenotypes: a population-based study

GeroScience

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ABSTRACT

Abstract Shorter leukocyte telomere length (LTL) is associated with cardiovascular dysfunction. Whether this association differs between measured and genetically predicted LTL is still unclear. Moreover, the molecular processes underlying the association remain largely unknown. We used baseline data of the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany [56.2% women, age: 55.5 ± 14.0 years (range 30 – 95 years)]. We calculated genetically predicted LTL in 4180 participants and measured LTL in a subset of 1828 participants with qPCR. Using multivariable regression, we examined the association of measured and genetically predicted LTL, and the difference between measured and genetically predicted LTL ( Δ LTL), with four vascular functional domains and the overall vascular health. Moreover, we performed epigenome-wide association studies of three LTL measures. Longer measured LTL was associated with better microvascular and cardiac function. Longer predicted LTL was associated with better cardiac function. Larger Δ LTL was associated with better microvascular and cardiac function and overall vascular health, independent of genetically predicted LTL. Several CpGs were associated ( p < 1e-05) with measured LTL ( n = 5), genetically predicted LTL ( n = 8), and Δ LTL ( n = 27). Genes whose methylation status was associated with Δ LTL were enriched in vascular endothelial signaling pathways and have been linked to environmental exposures, cardiovascular diseases, and mortality. Our findings suggest that non-genetic causes of LTL contribute to microvascular and cardiac function and overall vascular health, through an effect on the vascular endothelial signaling pathway. Interventions that counteract LTL may thus improve vascular function. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-023-00914-2. Keywords: Leukocyte telomere length, Polygenic risk score, Microvascular function, Cardiac function, Epigenome-wide association

CITATION EXPORT

Dan Liu, N Ahmad Aziz, Mohammed Aslam Imtiaz et al.. Associations of measured and genetically predicted leukocyte telomere length with vascular phenotypes: a population-based study. GeroScience. (2023). https://doi.org/10.1007/s11357-023-00914-2

AUTHORS

5 · 3 CENTRES

Dan Liu, N Ahmad Aziz, Mohammed Aslam Imtiaz, Gökhan Pehlivan, Monique M B Breteler

1German Center for Neurodegenerative Diseases (DZNE), Population Health Sciences, Bonn, Germany
2Department of Neurology, Faculty of Medicine, University of Bonn, Bonn, Germany
3Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Bonn, Germany