Polygenic basis and biomedical consequences of telomere length variation.

Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.

Defining background DNA levels found on the skin of children aged 0-5 years.

There are currently no data available regarding the normal levels of DNA found on the skin of children engaging in routine day to day activities to assist with the forensic interpretation of DNA profiles generated from skin surface swabs. To address this deficit, skin surface swab samples were collected from 12 face/neck sites and 20 body sites on 50 children less than 5 years old. After exclusion of spoilt samples, 60 sets of swabs from 47 children (30 face/neck, 30 body) comprising of 944 individual samples were analysed. The number of alleles observed which could have originated from the child and the number which must have come from another source (non-child) were analysed. The following variables were evaluated: age, kissing, feeding and washing practices, number of contacts and application of cream. Overall, extremely small amounts of non-child DNA were retrieved from skin swabs. Child only (46.3%) or no DNA at all (18.6%) was observed for 64.9% of all swabbed samples. Low levels of non-child DNA (1-5 alleles) were observed on 31.6% of all swabs tested with only 3.4% of swabs showing six or more alleles. A great deal of variation between children and between sites in the levels of both child DNA and non-child DNA was observed. A multilevel model, taking account of clustering within children, showed that there was a strong direct association between the amounts of child and non-child DNA observed. There was no relationship between the amount of DNA recovered and the demographic and biographic variables analysed. These background data have the potential to assist the analysis of DNA from the skin of children during criminal investigation.