TY - JOUR
T1 - Fat metabolism is associated with telomere length in six population-based studies
AU - van der Spek, Ashley
AU - Karamujić-čomić, Hata
AU - Pool, René
AU - Bot, Mariska
AU - Beekman, Marian
AU - Garmaeva, Sanzhima
AU - Arp, Pascal P
AU - Henkelman, Sandra
AU - Liu, Jun
AU - Alves, Alexessander Couto
AU - Willemsen, Gonneke
AU - Van Grootheest, Gerard
AU - Aubert, Geraldine
AU - Ikram, M Arfan
AU - Jarvelin, Marjo-riitta
AU - Lansdorp, Peter
AU - Uitterlinden, André G
AU - Zhernakova, Alexandra
AU - Slagboom, P Eline
AU - Penninx, Brenda W J H
AU - Boomsma, Dorret I
AU - Amin, Najaf
AU - Van Duijn, Cornelia M
AU - BBMRI Metabolomics Consortium
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
U2 - 10.1093/hmg/ddab281
DO - 10.1093/hmg/ddab281
M3 - Article
SN - 0964-6906
VL - 31
SP - 1159
EP - 1170
JO - Human molecular genetics
JF - Human molecular genetics
IS - 7
ER -
