Author:
van der Spek Ashley,Karamujić-Čomić Hata,Pool René,Bot Mariska,Beekman Marian,Garmaeva Sanzhima,Arp Pascal P,Henkelman Sandra,Liu Jun,Alves Alexessander Couto,Willemsen Gonneke,van Grootheest Gerard,Aubert Geraldine,Ikram M Arfan,Jarvelin Marjo-Riitta,Lansdorp Peter,Uitterlinden André G,Zhernakova Alexandra,Slagboom P Eline,Penninx Brenda W J H,Boomsma Dorret I,Amin Najaf,van Duijn Cornelia M,
Abstract
Abstract
Telomeres are repetitive DNA sequences located at the end of chromosomes, which are associated to biological aging, cardiovascular disease, cancer and mortality. Lipid and fatty acid metabolism have been associated with telomere shortening. We have conducted an in-depth study investigating the association of metabolic biomarkers with telomere length (LTL). We performed an association analysis of 226 metabolic biomarkers with LTL using data from 11 775 individuals from six independent population-based cohorts (BBMRI-NL consortium). Metabolic biomarkers include lipoprotein lipids and subclasses, fatty acids, amino acids, glycolysis measures and ketone bodies. LTL was measured by quantitative polymerase chain reaction or FlowFISH. Linear regression analysis was performed adjusting for age, sex, lipid-lowering medication and cohort-specific covariates (model 1) and additionally for body mass index (BMI) and smoking (model 2), followed by inverse variance-weighted meta-analyses (significance threshold Pmeta = 6.5 × 10−4). We identified four metabolic biomarkers positively associated with LTL, including two cholesterol to lipid ratios in small VLDL (S-VLDL-C % and S-VLDL-CE %) and two omega-6 fatty acid ratios (FAw6/FA and LA/FA). After additionally adjusting for BMI and smoking, these metabolic biomarkers remained associated with LTL with similar effect estimates. In addition, cholesterol esters in very small VLDL (XS-VLDL-CE) became significantly associated with LTL (P = 3.6 × 10−4). We replicated the association of FAw6/FA with LTL in an independent dataset of 7845 individuals (P = 1.9 × 10−4). To conclude, we identified multiple metabolic biomarkers involved in lipid and fatty acid metabolism that may be involved in LTL biology. Longitudinal studies are needed to exclude reversed causation.
Funder
European Union’s Seventh Framework Programme
Innovation-Oriented Research Program on Genomics
Centre for Medical Systems Biology and the Netherlands Consortium for Healthy Ageing
Netherlands Organization for Scientific Research
Publisher
Oxford University Press (OUP)
Subject
Genetics (clinical),Genetics,Molecular Biology,General Medicine
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