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

Veryan Codd, Christopher P. Nelson, Eva Albrecht, Massimo Mangino, Joris Deelen, Jessica L. Buxton, Jouke Jan Hottenga, Krista Fischer, Tõnu Esko, Ida Surakka, Linda Broer, Dale R. Nyholt, Irene Mateo Leach, Perttu Salo, Sara Hägg, Mary K. Matthews, Jutta Palmen, Giuseppe D. Norata, Paul F. O'Reilly, Danish SaleheenNajaf Amin, Anthony J. Balmforth, Marian Beekman, Rudolf A. De Boer, Stefan Böhringer, Peter S. Braund, Paul R. Burton, Anton J.Mde Craen, Matthew Denniff, Yanbin Dong, Konstantinos Douroudis, Elena Dubinina, Johan G. Eriksson, Katia Garlaschelli, Dehuang Guo, Anna Liisa Hartikainen, Anjali K. Henders, Jeanine J. Houwing-Duistermaat, Laura Kananen, Lennart C. Karssen, Johannes Kettunen, Norman Klopp, Vasiliki Lagou, Elisabeth M. Van Leeuwen, Pamela A. Madden, Reedik Mägi, Patrik K.E. Magnusson, Satu Männistö, Mark I. McCarthy, Sarah E. Medland, Evelin Mihailov, Grant W. Montgomery, Ben A. Oostra, Aarno Palotie, Annette Peters, Helen Pollard, Anneli Pouta, Inga Prokopenko, Samuli Ripatti, Veikko Salomaa, H. Eka D. Suchiman, Ana M. Valdes, Niek Verweij, Ana Viñuela, Xiaoling Wang, H. Erich Wichmann, Elisabeth Widen, Gonneke Willemsen, Margaret J. Wright, Kai Xia, Xiangjun Xiao, Dirk J. Van Veldhuisen, Alberico L. Catapano, Martin D. Tobin, Alistair S. Hall, Alexandra I.F. Blakemore, Wiek H. Van Gilst, Haidong Zhu, Jeanette Erdmann, Muredach P. Reilly, Sekar Kathiresan, Heribert Schunkert, Philippa J. Talmud, Nancy L. Pedersen, Markus Perola, Willem Ouwehand, Jaakko Kaprio, Nicholas G. Martin, Cornelia M. Van Duijn, Iiris Hovatta, Christian Gieger, Andres Metspalu, Dorret I. Boomsma, Marjo Riitta Jarvelin, P. Eline Slagboom, John R. Thompson, Tim D. Spector, Pim Van Der Harst, Nilesh J. Samani

Research output: Contribution to journalArticle

495 Scopus citations

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 × 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.

Original languageEnglish (US)
Pages (from-to)422-427
Number of pages6
JournalNature Genetics
Volume45
Issue number4
DOIs
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Genetics

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    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., Leach, I. M., Salo, P., Hägg, S., Matthews, M. K., Palmen, J., Norata, G. D., O'Reilly, P. F., ... Samani, N. J. (2013). Identification of seven loci affecting mean telomere length and their association with disease. Nature Genetics, 45(4), 422-427. https://doi.org/10.1038/ng.2528