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

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    Fulltext not available
    Authors
    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.
    Date
    2013
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Codd, V. and Nelson, C. and Albrecht, E. and Mangino, M. and Deelen, J. and Buxton, J. and Hottenga, J. et al. 2013. Identification of seven loci affecting mean telomere length and their association with disease. Nature Genetics. 45 (4): pp. 422-427.
    Source Title
    Nature Genetics
    DOI
    10.1038/ng.2528
    ISSN
    1061-4036
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/55728
    Collection
    • Curtin Research Publications
    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.

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