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

Nat. Genet. 45, 422-427 (2013)
Publ. Version/Full Text Volltext DOI
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Coronary-artery-disease ; Cardiovascular-disease ; Risk ; Cancer ; Atherosclerosis ; Susceptibility ; Fibroblasts ; Dysfunction ; Variants ; Stress
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 45, Issue: 4, Pages: 422-427 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed