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.; consortium, C. ARDIoGRAM; 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.

doi:10.1038/ng.2528

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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., et al. (2013). Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet, 45(4), 422/7, 427e1-2. doi:10.1038/ng.2528.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000B-A388-3 Version Permalink: https://hdl.handle.net/21.11116/0000-000C-088D-D

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https://www.ncbi.nlm.nih.gov/pubmed/23535734 (Any fulltext) Open Access status unknown

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Codd, V., Author
Nelson, C. P., Author
Albrecht, E., Author
Mangino, M., Author
Deelen, J.¹, Author
Buxton, J. L., Author
Hottenga, J. J., Author
Fischer, K., Author
Esko, T., Author
Surakka, I., Author
Broer, L., Author
Nyholt, D. R., Author
Mateo Leach, I., Author
Salo, P., Author
Hagg, S., Author
Matthews, M. K., Author
Palmen, J., Author
Norata, G. D., Author
O'Reilly, P. F., Author
Saleheen, D., Author
Amin, N., AuthorBalmforth, A. J., AuthorBeekman, M., Authorde Boer, R. A., AuthorBohringer, S., AuthorBraund, P. S., AuthorBurton, P. R., Authorde Craen, A. J., AuthorDenniff, M., AuthorDong, Y., AuthorDouroudis, K., AuthorDubinina, E., AuthorEriksson, J. G., AuthorGarlaschelli, K., AuthorGuo, D., AuthorHartikainen, A. L., AuthorHenders, A. K., AuthorHouwing-Duistermaat, J. J., AuthorKananen, L., AuthorKarssen, L. C., AuthorKettunen, J., AuthorKlopp, N., AuthorLagou, V., Authorvan Leeuwen, E. M., AuthorMadden, P. A., AuthorMagi, R., AuthorMagnusson, P. K., AuthorMannisto, S., AuthorMcCarthy, M. I., AuthorMedland, S. E., AuthorMihailov, E., AuthorMontgomery, G. W., AuthorOostra, B. A., AuthorPalotie, A., AuthorPeters, A., AuthorPollard, H., AuthorPouta, A., AuthorProkopenko, I., AuthorRipatti, S., AuthorSalomaa, V., AuthorSuchiman, H. E., AuthorValdes, A. M., AuthorVerweij, N., AuthorVinuela, A., AuthorWang, X., AuthorWichmann, H. E., AuthorWiden, E., AuthorWillemsen, G., AuthorWright, M. J., AuthorXia, K., AuthorXiao, X., Authorvan Veldhuisen, D. J., AuthorCatapano, A. L., AuthorTobin, M. D., AuthorHall, A. S., AuthorBlakemore, A. I., Authorvan Gilst, W. H., AuthorZhu, H., Authorconsortium, C. ARDIoGRAM, AuthorErdmann, J., AuthorReilly, M. P., AuthorKathiresan, S., AuthorSchunkert, H., AuthorTalmud, P. J., AuthorPedersen, N. L., AuthorPerola, M., AuthorOuwehand, W., AuthorKaprio, J., AuthorMartin, N. G., Authorvan Duijn, C. M., AuthorHovatta, I., AuthorGieger, C., AuthorMetspalu, A., AuthorBoomsma, D. I., AuthorJarvelin, M. R., AuthorSlagboom, P. E., Author Thompson, J. R., AuthorSpector, T. D., Authorvan der Harst, P., AuthorSamani, N. J., Author more..

Affiliations:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006

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Free keywords: Biomarkers, Tumor/*genetics 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

Abstract: 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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Dates: Published Online: 2013-04Date issued: 2013-03-29

Publication Status: Issued

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Identifiers: Other: 23535734
DOI: 10.1038/ng.2528
ISSN: 1546-1718 (Electronic)1061-4036 (Linking)

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Title: Nat Genet

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Pages: - Volume / Issue: 45 (4) Sequence Number: - Start / End Page: 422/7, 427e1 - 2 Identifier: -