Identification of seven loci affecting mean telomere length and their association with disease
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, inclu...
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| Format: | Journal Article |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/55728 |
| _version_ | 1848759692647464960 |
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| author | Codd, V. Nelson, C. Albrecht, E. Mangino, M. Deelen, J. Buxton, J. Hottenga, J. Fischer, K. Esko, T. Surakka, I. Broer, L. Nyholt, D. Leach, I. Salo, P. Hägg, S. Matthews, M. Palmen, J. Norata, Giuseppe O'Reilly, P. Saleheen, D. Amin, N. Balmforth, A. Beekman, M. De Boer, R. Böhringer, S. Braund, P. Burton, P. Craen, A. Denniff, M. Dong, Y. Douroudis, K. Dubinina, E. Eriksson, J. Garlaschelli, K. Guo, D. Hartikainen, A. Henders, A. Houwing-Duistermaat, J. Kananen, L. Karssen, L. Kettunen, J. Klopp, N. Lagou, V. Van Leeuwen, E. Madden, P. Mägi, R. Magnusson, P. Männistö, S. McCarthy, M. Medland, S. Mihailov, E. Montgomery, G. Oostra, B. Palotie, A. Peters, A. Pollard, H. Pouta, A. Prokopenko, I. Ripatti, S. Salomaa, V. Suchiman, H. Valdes, A. Verweij, N. Viñuela, A. Wang, X. Wichmann, H. Widen, E. Willemsen, G. Wright, M. Xia, K. Xiao, X. Van Veldhuisen, D. |
| author_facet | Codd, V. Nelson, C. Albrecht, E. Mangino, M. Deelen, J. Buxton, J. Hottenga, J. Fischer, K. Esko, T. Surakka, I. Broer, L. Nyholt, D. Leach, I. Salo, P. Hägg, S. Matthews, M. Palmen, J. Norata, Giuseppe O'Reilly, P. Saleheen, D. Amin, N. Balmforth, A. Beekman, M. De Boer, R. Böhringer, S. Braund, P. Burton, P. Craen, A. Denniff, M. Dong, Y. Douroudis, K. Dubinina, E. Eriksson, J. Garlaschelli, K. Guo, D. Hartikainen, A. Henders, A. Houwing-Duistermaat, J. Kananen, L. Karssen, L. Kettunen, J. Klopp, N. Lagou, V. Van Leeuwen, E. Madden, P. Mägi, R. Magnusson, P. Männistö, S. McCarthy, M. Medland, S. Mihailov, E. Montgomery, G. Oostra, B. Palotie, A. Peters, A. Pollard, H. Pouta, A. Prokopenko, I. Ripatti, S. Salomaa, V. Suchiman, H. Valdes, A. Verweij, N. Viñuela, A. Wang, X. Wichmann, H. Widen, E. Willemsen, G. Wright, M. Xia, K. Xiao, X. Van Veldhuisen, D. |
| author_sort | Codd, V. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T10:03:56Z |
| format | Journal Article |
| id | curtin-20.500.11937-55728 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:03:56Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-557282018-03-29T09:09:36Z Identification of seven loci affecting mean telomere length and their association with disease Codd, V. Nelson, C. Albrecht, E. Mangino, M. Deelen, J. Buxton, J. Hottenga, J. Fischer, K. Esko, T. Surakka, I. Broer, L. Nyholt, D. Leach, I. Salo, P. Hägg, S. Matthews, M. Palmen, J. Norata, Giuseppe O'Reilly, P. Saleheen, D. Amin, N. Balmforth, A. Beekman, M. De Boer, R. Böhringer, S. Braund, P. Burton, P. Craen, A. Denniff, M. Dong, Y. Douroudis, K. Dubinina, E. Eriksson, J. Garlaschelli, K. Guo, D. Hartikainen, A. Henders, A. Houwing-Duistermaat, J. Kananen, L. Karssen, L. Kettunen, J. Klopp, N. Lagou, V. Van Leeuwen, E. Madden, P. Mägi, R. Magnusson, P. Männistö, S. McCarthy, M. Medland, S. Mihailov, E. Montgomery, G. Oostra, B. Palotie, A. Peters, A. Pollard, H. Pouta, A. Prokopenko, I. Ripatti, S. Salomaa, V. Suchiman, H. Valdes, A. Verweij, N. Viñuela, A. Wang, X. Wichmann, H. Widen, E. Willemsen, G. Wright, M. Xia, K. Xiao, X. Van Veldhuisen, D. 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. 2013 Journal Article http://hdl.handle.net/20.500.11937/55728 10.1038/ng.2528 Nature Publishing Group restricted |
| spellingShingle | Codd, V. Nelson, C. Albrecht, E. Mangino, M. Deelen, J. Buxton, J. Hottenga, J. Fischer, K. Esko, T. Surakka, I. Broer, L. Nyholt, D. Leach, I. Salo, P. Hägg, S. Matthews, M. Palmen, J. Norata, Giuseppe O'Reilly, P. Saleheen, D. Amin, N. Balmforth, A. Beekman, M. De Boer, R. Böhringer, S. Braund, P. Burton, P. Craen, A. Denniff, M. Dong, Y. Douroudis, K. Dubinina, E. Eriksson, J. Garlaschelli, K. Guo, D. Hartikainen, A. Henders, A. Houwing-Duistermaat, J. Kananen, L. Karssen, L. Kettunen, J. Klopp, N. Lagou, V. Van Leeuwen, E. Madden, P. Mägi, R. Magnusson, P. Männistö, S. McCarthy, M. Medland, S. Mihailov, E. Montgomery, G. Oostra, B. Palotie, A. Peters, A. Pollard, H. Pouta, A. Prokopenko, I. Ripatti, S. Salomaa, V. Suchiman, H. Valdes, A. Verweij, N. Viñuela, A. Wang, X. Wichmann, H. Widen, E. Willemsen, G. Wright, M. Xia, K. Xiao, X. Van Veldhuisen, D. Identification of seven loci affecting mean telomere length and their association with disease |
| title | Identification of seven loci affecting mean telomere length and their association with disease |
| title_full | Identification of seven loci affecting mean telomere length and their association with disease |
| title_fullStr | Identification of seven loci affecting mean telomere length and their association with disease |
| title_full_unstemmed | Identification of seven loci affecting mean telomere length and their association with disease |
| title_short | Identification of seven loci affecting mean telomere length and their association with disease |
| title_sort | identification of seven loci affecting mean telomere length and their association with disease |
| url | http://hdl.handle.net/20.500.11937/55728 |