Document Detail


Identification of seven loci affecting mean telomere length and their association with disease.
MedLine Citation:
PMID:  23535734     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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 Saleheen; Najaf Amin; Anthony J Balmforth; Marian Beekman; Rudolf A de Boer; Stefan Böhringer; Peter S Braund; Paul R Burton; Anton J M de 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; Cardiogram Consortium; 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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature genetics     Volume:  45     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-28     Completed Date:  2013-05-21     Revised Date:  2014-06-10    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  422-7, 427e1-2     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Case-Control Studies
Disease / genetics*
Female
Genetic Loci / genetics*
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Leukocytes / metabolism*
Male
Meta-Analysis as Topic
Risk Factors
Telomerase / genetics*
Telomere / genetics*
Tumor Markers, Biological / genetics*
Grant Support
ID/Acronym/Agency:
090532//Wellcome Trust; G0902313//Medical Research Council; R56 DA012854/DA/NIDA NIH HHS; RG/08/014/24067//British Heart Foundation
Chemical
Reg. No./Substance:
0/Tumor Markers, Biological; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase
Comments/Corrections

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