Identification of seven loci affecting mean telomere length and their association with disease

Codd, V., Nelson, C. P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J. L., Hottenga, J. J., Fischer, K., Esko, T., Surakka, I., Broer, L., Nyholt, D.R., Mateo Leach, I., Salo, P., Hagg, S., Matthews, M. K., Palmen, J., Norata, G. D., O'Reilly, P. F., Saleheen, D., Amin, N., Balmforth, A. J., Beekman, M., de Boer, R. A., Bohringer, S., Braund, P. S., Burton, P. R., de Craen, A. J., Denniff, M., Dong, Y., Douroudis, K., Dubinina, E., Eriksson, J. G., Garlaschelli, K., Guo, D., Hartikainen, A. L., Henders, A. K., Houwing-Duistermaat, J. J., Kananen, L., Karssen, L. C., Kettunen, J., Klopp, N., Lagou, V., van Leeuwen, E. M., Madden, P. A., Magi, R., Magnusson, P. K., Mannisto, S., McCarthy, M. I., Medland, S. E., Mihailov, E., Montgomery, G. W., Oostra, B. A., Palotie, A., Peters, A., Pollard, H., Pouta, A., Prokopenko, I., Ripatti, S., Salomaa, V., Suchiman, H. E., Valdes, A. M., Verweij, N., Vinuela, A., Wang, X., Wichmann, H. E., Widen, E., Willemsen, G., Wright, M. J., Xia, K., Xiao, X., van Veldhuisen, D. J., Catapano, A. L., Tobin, M. D., Hall, A. S., Blakemore, A. I., van Gilst, W. H., Zhu, H., Erdmann, J., Reilly, M. P., Kathiresan, S., Schunkert, H., Talmud, P. J., Pedersen, N. L., Perola, M., Ouwehand, W., Kaprio, J., Martin, N. G., van Duijn, C. M., Hovatta, I., Gieger, C., Metspalu, A., Boomsma, D. I., Jarvelin, M. R., Slagboom, P. E., Thompson, J. R., Spector, T. D., van der Harst, P., & Samani, N. J. (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nature Genetics, 45(4), pp. 422-427.

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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 x 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.

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ID Code: 91832
Item Type: Journal Article
Refereed: Yes
Keywords: Case-Control Studies, Disease/*genetics, Female, Genetic Loci/*genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukocytes/*metabolism, Male, Meta-Analysis as Topic, Risk Factors, Telomerase/*genetics, Telomere/*genetics, Tumor Markers, Biological/*genetics
DOI: 10.1038/ng.2528
ISSN: 1546-1718
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 14 Jan 2016 01:57
Last Modified: 18 Jan 2016 01:06

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