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

Veryan Codd; Christopher P. Nelson; Eva Albrecht; Massimo Mangino; Joris Deelen; Jessica L. Buxton; Jouke Jan Hottenga; Krista Fischer; Tonu Esko; Ida Surakka; Linda Broer; Dale R. Nyholt; Irene Mateo Leach; Perttu Salo; Sara Hagg; 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 Bohringer; 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 Maegi; Patrik K. E. Magnusson; Satu Mannisto; 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 Vinuela; 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; 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; Iris 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; CARDIoGRAM Consortium

doi:10.1038/ng.2528

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

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

Veryan Codd, Christopher P. Nelson, Eva Albrecht, Massimo Mangino, Joris Deelen, Jessica L. Buxton, Jouke Jan Hottenga, Krista Fischer, Tonu Esko, Ida Surakka, …

Nature genetics, Vol.45(4), pp.422-427

01/04/2013

DOI: https://doi.org/10.1038/ng.2528

PMID: 23535734

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 x 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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Title: Identification of seven loci affecting mean telomere length and their association with disease
Creators: Veryan Codd - University of Leicester
Christopher P. Nelson - University of Leicester
Eva Albrecht - Helmholtz Zentrum München
Massimo Mangino - King's College London
Joris Deelen - Leiden University Medical Center
Jessica L. Buxton - Imperial College London
Jouke Jan Hottenga - University of Amsterdam
Krista Fischer - University of Tartu
Tonu Esko - University of Tartu
Ida Surakka - Institute for Molecular Medicine Finland
Linda Broer - Netherlands Consortium for Healthy Ageing
Dale R. Nyholt - QIMR Berghofer Medical Research Institute
Irene Mateo Leach - University Medical Center Groningen
Perttu Salo - Finnish Institute for Health and Welfare
Sara Hagg - Karolinska Institutet
Mary K. Matthews - University of Leicester
Jutta Palmen - UCL, Inst Cardiovasc Sci, London, England
Giuseppe D. Norata - University of Milan
Paul F. O'Reilly - University of London
Danish Saleheen - University of Cambridge
Najaf Amin - Erasmus MC
Anthony J. Balmforth - University of Leeds
Marian Beekman - Leiden University Medical Center
Rudolf A. de Boer - University Medical Center Groningen
Stefan Bohringer - Leiden University Medical Center
Peter S. Braund - University of Leicester
Paul R. Burton - University of Leicester
Anton J. M. de Craen - Leiden University
Matthew Denniff - University of Leicester
Yanbin Dong - Prevention Institute
Konstantinos Douroudis - University of Tartu
Elena Dubinina - University of Leicester
Johan G. Eriksson - Finnish Institute for Health and Welfare
Katia Garlaschelli - Ospedale Bassini
Dehuang Guo - Prevention Institute
Anna-Liisa Hartikainen - University of Oulu
Anjali K. Henders - QIMR Berghofer Medical Research Institute
Jeanine J. Houwing-Duistermaat - Leiden University
Laura Kananen - University of Helsinki
Lennart C. Karssen - Erasmus MC
Johannes Kettunen - University of Helsinki
Norman Klopp - Helmholtz Zentrum München
Vasiliki Lagou - Oxford Centre for Diabetes, Endocrinology and Metabolism
Elisabeth M. van Leeuwen - Erasmus MC
Pamela A. Madden - Washington University in St. Louis
Reedik Maegi - University of Tartu
Patrik K. E. Magnusson - Karolinska Institutet
Satu Mannisto - Finnish Institute for Health and Welfare
Mark I. McCarthy - Oxford Centre for Diabetes, Endocrinology and Metabolism
Sarah E. Medland - QIMR Berghofer Medical Research Institute
Evelin Mihailov - University of Tartu
Grant W. Montgomery - QIMR Berghofer Medical Research Institute
Ben A. Oostra - Erasmus MC
Aarno Palotie - Wellcome Sanger Institute
Annette Peters - Helmholtz Zentrum München
Helen Pollard - University of Leicester
Anneli Pouta - University of Oulu
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Samuli Ripatti - Finnish Institute for Health and Welfare
Veikko Salomaa - Finnish Institute for Health and Welfare
H. Eka D. Suchiman - Leiden University Medical Center
Ana M. Valdes - King's College London
Niek Verweij - University Medical Center Groningen
Ana Vinuela - King's College London
Xiaoling Wang - Prevention Institute
H-Erich Wichmann - Helmholtz Zentrum München
Elisabeth Widen - Institute for Molecular Medicine Finland
Gonneke Willemsen - Vrije Universiteit Amsterdam
Margaret J. Wright - QIMR Berghofer Medical Research Institute
Kai Xia - University of North Carolina at Chapel Hill
Xiangjun Xiao - The University of Texas MD Anderson Cancer Center
Dirk J. van Veldhuisen - University Medical Center Groningen
Alberico L. Catapano - University of Milan
Martin D. Tobin - University of Leicester
Alistair S. Hall - University of Leeds
Alexandra I. F. Blakemore - Imperial College London
Wiek H. van Gilst - University Medical Center Groningen
Haidong Zhu - Prevention Institute
Jeanette Erdmann - University of Lübeck
Muredach P. Reilly - Cardiovascular Institute of the South
Sekar Kathiresan - Massachusetts General Hospital
Heribert Schunkert - University of Lübeck
Philippa J. Talmud - UCL, Inst Cardiovasc Sci, London, England
Nancy L. Pedersen - Karolinska Institutet
Markus Perola - Finnish Institute for Health and Welfare
Willem Ouwehand - Wellcome Sanger Institute
Jaakko Kaprio - Institute for Molecular Medicine Finland
Nicholas G. Martin - QIMR Berghofer Medical Research Institute
Cornelia M. van Duijn - Centre for Medical Systems Biology
Iris Hovatta - University of Helsinki
Christian Gieger - Helmholtz Zentrum München
Andres Metspalu - University of Tartu
Dorret I. Boomsma - Vrije Universiteit Amsterdam
Marjo-Riitta Jarvelin - University of London
P. Eline Slagboom - Leiden University Medical Center
John R. Thompson - University of Leicester
Tim D. Spector - King's College London
Pim van der Harst - University Medical Center Groningen
Nilesh J. Samani - Glenfield Hospital
CARDIoGRAM Consortium
Publication Details: Nature genetics, Vol.45(4), pp.422-427
Publisher: Springer Nature
Number of pages: 6
Date published: 01/04/2013
Grant note: HEALTH-F4-2007-201413 / European Union Framework 7 ENGAGE Project G0801056B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission R56DA012854 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission NF-SI-0611-10170 / National Institute for Health Research; National Institute for Health Research (NIHR) MR/K014536/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 99928791402346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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