Telomeres are structures at the ends of eukaryotic chromosomes that are involved in maintaining genomic stability and regulating cellular proliferation. In somatic cells telomere length progressively shortens with each mitotic division due to the inability of DNA polymerase to fully replicate the 3’ end of the DNA strand. Telomere length subsequently declines with age and is seen as a marker of biological age and shorter mean leukocyte telomere length has been shown to be associated with risk of several age-related diseases. In certain cell types (e.g. germ cells) telomere length is maintained by the enzyme telomerase, a ribonucleoprotein consisting of a reverse transcriptase (TERT) and a RNA template (TERC). Telomerase re-activation in somatic cells can contribute to the pathogenesis of several cancers.
TL has a strong genetic determination with heritability estimates ranging from 44-80%. In order to identify genetic variants that affect TL we conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 subjects and follow-up replication analyses in 9,492 individuals. This identified a locus on 3q26 encompassing the telomerase RNA component TERC, with compelling evidence for association with mean telomere length. Each copy of the minor allele was associated with ˜75 base pairs shorter mean telomere length which is equivalent to ˜3.6 years of age-related attrition in telomere length.
Given the importance of telomeres in nuclear and cellular function and the central role of telomere length in determining telomere function, our finding could have broad relevance for both normal and pathological age-associated processes.
Codd V, Mangino M, van der Harst P, Braund PS, Kaiser M, Beveridge AJ, Rafelt S, Moore J, Nelson C, Soranzo N, Zhai G, Valdes AM, Blackburn H, Mateo Leach I, de Boer RA; Wellcome Trust Case Control Consortium, Goodall AH, Ouwehand W, van Veldhuisen DJ, van Gilst WH, Navis G, Burton PR, Tobin MD, Hall AS, Thompson JR, Spector T, Samani NJ. Chr. Common variants near TERC are associated with mean telomere length. Nature Genetics 2010.