Human leukocyte telomere length is associated with DNA methylation levels in multiple subtelomeric and imprinted loci

In humans, leukocyte telomere length (LTL) is positively correlated with lifespan, and shorter LTL is associated with increased risk of age-related disease. In this study we tested for association between telomere length and methylated cytosine levels. Measurements of mean telomere length and DNA methylation at .450,000 CpG sites were obtained for both blood (N 5 24) and EBV-transformed cell-line (N 5 36) DNA samples from men aged 44–45 years. We identified 65 gene promoters enriched for CpG sites at which methylation levels are associated with leukocyte telomere length, and 36 gene promoters enriched for CpG sites at which methylation levels are associated with telomere length in DNA from EBV-transformed cell-lines.Weobserved significant enrichment of positively associated methylated CpG sites in subtelomeric loci (within 4 Mb of the telomere) (P , 0.01), and also at loci in imprinted regions (P , 0.001). Our results pave the way for further investigations to help elucidate the relationships between telomere length, DNA methylation and gene expression in health and disease.The Section of Investigative Medicine at Imperial College London is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, and FP7- HEALTH- 2009- 241592 EuroCHIP grant and is supported by the NIHR www.nature.com/scientificreports SCIENTIFIC REPORTS | 4 : 4954 | DOI: 10.1038/srep04954 7 Imperial Biomedical Research Centre Funding Scheme. For the 1958 Birth Cohort samples, venous blood collection was funded by the UK Medical Research Council (G0000934) and cell-line production, DNA extraction and processing by the Wellcome Trust (068545/Z/ 02). MS was supported by a grant from the Canadian Institute for Health Research MOP-42411. This work was also funded by aWellcome Trust programme grant 072937/Z/ 03/Z awarded to MP, and a Wellcome Trust fellowship grant, WT088431MA, held by JLB