Identification of seven loci affecting mean telomere length and their association with disease
Access Status
Authors
Date
2013Type
Metadata
Show full item recordAbstract
Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 × 10 -8). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.
Citation
Source Title
DOI
ISSN
School
Collection
Related items
Showing items related by title, author, creator and subject.
-
Zhang, J.; Rane, G.; Dai, X.; Shanmugam, M.; Arfuso, Frank; Samy, R.; Lai, M.; Kappei, D.; Kumar, Alan Prem; Sethi, G. (2016)© 2015 Elsevier B.V. Telomeres are the heterochromatic repeat regions at the ends of eukaryotic chromosomes, whose length is considered to be a determinant of biological ageing. Normal ageing itself is associated with ...
-
Baragetti, A.; Palmen, J.; Garlaschelli, K.; Grigore, L.; Pellegatta, F.; Tragni, E.; Catapano, A.; Humphries, S.; Norata, Giuseppe; Talmud, P. (2015)© 2014 The Association for the Publication of the Journal of Internal Medicine. Introduction: Leucocyte telomere length (LTL) is an important determinant of telomere function and cellular replicative capacity. The aim of ...
-
Law, M.; Bishop, D.; Lee, J.; Brossard, M.; Martin, N.; Moses, Eric; Song, F.; Barrett, J.; Kumar, R.; Easton, D.; Pharoah, P.; Swerdlow, A.; Kypreou, K.; Taylor, J.; Harland, M.; Randerson-Moor, J.; Akslen, L.; Andresen, P.; Avril, M.; Azizi, E.; Scarrà, G.; Brown, K.; Debniak, T.; Duffy, D.; Elder, D.; Fang, S.; Friedman, E.; Galan, P.; Ghiorzo, P.; Gillanders, E.; Goldstein, A.; Gruis, N.; Hansson, J.; Helsing, P.; Hocevar, M.; Höiom, V.; Ingvar, C.; Kanetsky, P.; Chen, W.; Landi, M.; Lang, J.; Lathrop, G.; Lubinski, J.; MacKie, R.; Mann, G.; Molven, A.; Montgomery, G.; Novakovic, S.; Olsson, H.; Puig, S.; Puig-Butille, J.; Qureshi, A.; Radford-Smith, G.; Van Der Stoep, N.; Van Doorn, R.; Whiteman, D.; Craig, J.; Schadendorf, D.; Simms, L.; Burdon, K.; Nyholt, D.; Pooley, K.; Orr, N.; Stratigos, A.; Cust, A.; Ward, S.; Hayward, N.; Han, J.; Schulze, H.; Dunning, A.; Bishop, J.; Demenais, F.; Amos, C.; MacGregor, S.; Iles, M. (2015)Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). ...