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Document type:
Journal Article; Research Support, Non-U.S. Gov't
Author(s):
Codd, Veryan; Nelson, Christopher P; Albrecht, Eva; Mangino, Massimo; Deelen, Joris; Buxton, Jessica L; Hottenga, Jouke Jan; Fischer, Krista; Esko, Tõnu; Surakka, Ida; Broer, Linda; Nyholt, Dale R; Mateo Leach, Irene; Salo, Perttu; Hägg, Sara; Matthews, Mary K; Palmen, Jutta; Norata, Giuseppe D; O'Reilly, Paul F; Saleheen, Danish; Amin, Najaf; Balmforth, Anthony J; Beekman, Marian; de Boer, Rudolf A; Böhringer, Stefan; Braund, Peter S; Burton, Paul R; de Craen, Anton J M; Denniff, Matthew; Dong,...     »
Title:
Identification of seven loci affecting mean telomere length and their association with disease.
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.
Journal title abbreviation:
Nat Genet
Year:
2013
Journal volume:
45
Journal issue:
4
Pages contribution:
422-7, 427e1-2
Language:
eng
Fulltext / DOI:
doi:10.1038/ng.2528
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/23535734
Print-ISSN:
1061-4036
TUM Institution:
Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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