Identification of seven loci affecting mean telomere length and their association with disease (original) (raw)

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Acknowledgements

This study was undertaken under the framework of European Union Framework 7 ENGAGE Project (HEALTH-F4-2007-201413). A full list of acknowledgments, including support for each study, is provided in the Supplementary Note.

Author information

Author notes

1. Veryan Codd, Christopher P Nelson, Eva Albrecht, Massimo Mangino and Pim van der Harst: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
   Veryan Codd, Christopher P Nelson, Mary K Matthews, Peter S Braund, Matthew Denniff, Elena Dubinina, Helen Pollard, Pim van der Harst & Nilesh J Samani
2. National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK
   Veryan Codd, Christopher P Nelson & Nilesh J Samani
3. Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
   Eva Albrecht & Christian Gieger
4. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
   Massimo Mangino, Ana M Valdes, Ana Viñuela & Tim D Spector
5. Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
   Joris Deelen, Marian Beekman, H Eka D Suchiman & P Eline Slagboom
6. Netherlands Consortium for Healthy Aging, Leiden University Medical Center, Leiden, The Netherlands
   Joris Deelen, Linda Broer, Marian Beekman, Jeanine J Houwing-Duistermaat, Cornelia M van Duijn & P Eline Slagboom
7. Section of Investigative Medicine, Imperial College London, London, UK
   Jessica L Buxton & Alexandra I F Blakemore
8. Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, The Netherlands
   Jouke Jan Hottenga, Gonneke Willemsen & Dorret I Boomsma
9. Estonian Genome Center, University of Tartu, Tartu, Estonia
   Krista Fischer, Tõnu Esko, Konstantinos Douroudis, Reedik Mägi, Evelin Mihailov, Markus Perola & Andres Metspalu
10. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
    Ida Surakka, Johannes Kettunen, Samuli Ripatti, Elisabeth Widen, Markus Perola & Jaakko Kaprio
11. Department of Chronic Disease Prevention, Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
    Ida Surakka, Perttu Salo, Johan G Eriksson, Johannes Kettunen, Satu Männistö, Samuli Ripatti, Veikko Salomaa & Markus Perola
12. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
    Linda Broer, Najaf Amin, Lennart C Karssen, Elisabeth M van Leeuwen, Ben A Oostra & Cornelia M van Duijn
13. Centre for Medical Systems Biology, Leiden, The Netherlands
    Linda Broer & Cornelia M van Duijn
14. Queensland Institute of Medical Research, Brisbane, Australia
    Dale R Nyholt, Anjali K Henders, Sarah E Medland, Grant W Montgomery, Margaret J Wright & Nicholas G Martin
15. Department of Cardiology, University of Groningen, University Medical Center, Groningen, The Netherlands
    Irene Mateo Leach, Rudolf A de Boer, Niek Verweij, Dirk J van Veldhuisen, Wiek H van Gilst & Pim van der Harst
16. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Sara Hägg, Patrik K E Magnusson & Nancy L Pedersen
17. Institute of Cardiovascular Science, Univerisity College London, London, UK
    Jutta Palmen & Philippa J Talmud
18. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
    Giuseppe D Norata & Alberico L Catapano
19. Centro Societa Italiana per lo Studio dell'Aterosclerosi, Bassini Hospital, Cinisello B, Italy
    Giuseppe D Norata & Katia Garlaschelli
20. The Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University, London, UK
    Giuseppe D Norata
21. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK
    Paul F O'Reilly & Marjo-Riitta Jarvelin
22. Medical Research Council–Health Protection Agency Centre for Environment and Health, Faculty of Medicine, Imperial College London, London, UK
    Paul F O'Reilly & Marjo-Riitta Jarvelin
23. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
    Danish Saleheen
24. Center for Non-Communicable Diseases, Karachi, Pakistan
    Danish Saleheen
25. Division of Epidemiology, Leeds Institute of Genetics, Health and Therapeutics, School of Medicine, University of Leeds, Leeds, UK
    Anthony J Balmforth & Alistair S Hall
26. Section of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
    Stefan Böhringer & Jeanine J Houwing-Duistermaat
27. Department of Health Sciences, University of Leicester, Leicester, UK
    Paul R Burton, Martin D Tobin & John R Thompson
28. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
    Anton J Mde Craen
29. Georgia Prevention Institute, Georgia Health Sciences University, Augusta, Georgia, USA
    Yanbin Dong, Dehuang Guo, Xiaoling Wang & Haidong Zhu
30. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
    Johan G Eriksson
31. Folkhälsan Research Center, Helsinki, Finland
    Johan G Eriksson
32. Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland
    Johan G Eriksson
33. Institute of Clinical Medicine/Obstetrics and Gynecology, University of Oulu, Oulu, Finland
    Anna-Liisa Hartikainen & Anneli Pouta
34. Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    Laura Kananen & Iiris Hovatta
35. Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
    Laura Kananen & Iiris Hovatta
36. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
    Norman Klopp & Annette Peters
37. Hanover Unified Biobank, Hanover Medical School, Hanover, Germany
    Norman Klopp
38. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
    Vasiliki Lagou, Mark I McCarthy & Inga Prokopenko
39. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
    Pamela A Madden
40. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    Mark I McCarthy
41. Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK
    Mark I McCarthy
42. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
    Aarno Palotie, Samuli Ripatti & Willem Ouwehand
43. Department of Medical Genetics, University of Helsinki and the Helsinki University Hospital, Helsinki, Finland
    Aarno Palotie
44. Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
    Annette Peters
45. Munich Heart Alliance, Munich, Germany
    Annette Peters
46. National Institute for Health and Welfare, Oulu, Finland
    Anneli Pouta
47. Institute of Epidemiology I, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
    H-Erich Wichmann
48. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig Maximilians Universität, Munich, Germany
    H-Erich Wichmann
49. KlinikumGrosshadern, Munich, Germany
    H-Erich Wichmann
50. Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA
    Kai Xia
51. Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Xiangjun Xiao
52. Instituto di Ricovero e Cura a Carattere Scientifico Multimedica, Milan, Italy
    Alberico L Catapano
53. UniversitätzuLübeck, Medizinische Klinik II, Lübeck, Germany
    Jeanette Erdmann & Heribert Schunkert
54. The Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Muredach P Reilly
55. Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA
    Sekar Kathiresan
56. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Sekar Kathiresan
57. Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA
    Sekar Kathiresan
58. Department of Hematology, University of Cambridge, Cambridge, UK
    Willem Ouwehand
59. National Health Service Blood and Transplant, Cambridge, UK
    Willem Ouwehand
60. Department of Public Health, University of Helsinki, Hjelt Institute, Helsinki, Finland
    Jaakko Kaprio
61. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
    Jaakko Kaprio & Iiris Hovatta
62. Institute of Health Sciences, University of Oulu, Oulu, Finland
    Marjo-Riitta Jarvelin
63. Biocenter Oulu, University of Oulu, Oulu, Finland
    Marjo-Riitta Jarvelin
64. Department of Lifecourse and Services, National Institute for Health and Welfare, Oulu, Finland
    Marjo-Riitta Jarvelin
65. Department of Genetics, University of Groningen, University Medical Center, Groningen, The Netherlands
    Pim van der Harst

Authors

1. Veryan Codd
2. Christopher P Nelson
3. Eva Albrecht
4. Massimo Mangino
5. Joris Deelen
6. Jessica L Buxton
7. Jouke Jan Hottenga
8. Krista Fischer
9. Tõnu Esko
10. Ida Surakka
11. Linda Broer
12. Dale R Nyholt
13. Irene Mateo Leach
14. Perttu Salo
15. Sara Hägg
16. Mary K Matthews
17. Jutta Palmen
18. Giuseppe D Norata
19. Paul F O'Reilly
20. Danish Saleheen
21. Najaf Amin
22. Anthony J Balmforth
23. Marian Beekman
24. Rudolf A de Boer
25. Stefan Böhringer
26. Peter S Braund
27. Paul R Burton
28. Anton J Mde Craen
29. Matthew Denniff
30. Yanbin Dong
31. Konstantinos Douroudis
32. Elena Dubinina
33. Johan G Eriksson
34. Katia Garlaschelli
35. Dehuang Guo
36. Anna-Liisa Hartikainen
37. Anjali K Henders
38. Jeanine J Houwing-Duistermaat
39. Laura Kananen
40. Johannes Kettunen
41. Norman Klopp
42. Vasiliki Lagou
43. Elisabeth M van Leeuwen
44. Pamela A Madden
45. Reedik Mägi
46. Patrik K E Magnusson
47. Satu Männistö
48. Mark I McCarthy
49. Sarah E Medland
50. Evelin Mihailov
51. Grant W Montgomery
52. Ben A Oostra
53. Aarno Palotie
54. Annette Peters
55. Helen Pollard
56. Anneli Pouta
57. Inga Prokopenko
58. Samuli Ripatti
59. Veikko Salomaa
60. H Eka D Suchiman
61. Ana M Valdes
62. Niek Verweij
63. Ana Viñuela
64. Xiaoling Wang
65. H-Erich Wichmann
66. Elisabeth Widen
67. Gonneke Willemsen
68. Margaret J Wright
69. Kai Xia
70. Xiangjun Xiao
71. Dirk J van Veldhuisen
72. Alberico L Catapano
73. Martin D Tobin
74. Alistair S Hall
75. Alexandra I F Blakemore
76. Wiek H van Gilst
77. Haidong Zhu
78. Jeanette Erdmann
79. Muredach P Reilly
80. Sekar Kathiresan
81. Heribert Schunkert
82. Philippa J Talmud
83. Nancy L Pedersen
84. Markus Perola
85. Willem Ouwehand
86. Jaakko Kaprio
87. Nicholas G Martin
88. Cornelia M van Duijn
89. Iiris Hovatta
90. Christian Gieger
91. Andres Metspalu
92. Dorret I Boomsma
93. Marjo-Riitta Jarvelin
94. P Eline Slagboom
95. John R Thompson
96. Tim D Spector
97. Pim van der Harst
98. Nilesh J Samani

Consortia

CARDIoGRAM consortium

Contributions

V.C. and N.J.S. supervised the overall study. V.C., M.M., T.D.S., P.v.d.H. and N.J.S. designed the study. M.M., T.E., D.R.N., R.A.d.B., G.D.N., D.S., N.A., A.J.B., P.S.B., P.R.B., K.D., M.D., J.G.E., K.G., A.-L.H., A.K.H., L.C. Karssen, J.K., N.K., V.L., I.M.L., E.M.v.L., P.A.M., R.M., P.K.E.M., S.M., M.I.M., S.E.M., E.M., G.W.M., B.A.O., J.P., A. Palotie, A. Peters, Anneli Pouta, I.P., S.R.,V.S., A.M.V., N.V., A.V., H.-E.W., E.W., G.W., M.J.W., K.X., X.X., D.J.v.V., A.L.C., M.D.T., A.S.H., A.I.F.B., P.J.T., N.L.P., M.P., J.D., W.O., J. Kaprio, N.G.M., C.M.v.D., C.G., A.M., D.I.B., M.-R.J., W.H.v.G., P.E.S., T.D.S., P.v.d.H. and N.J.S. contributed to recruitment, study and data management, genotyping and/or imputation of individual studies. V.C., J.L.B., M.K.M., R.A.d.B., J.P., E.D., L.K., H.P., P.T.J. and I.H. measured telomere length. C.P.N., E.A., M.M., J.D., J.L.B., J.J.H., K.F., T.E., I.S., L.B., D.R.N., R.A.d.B., P.S., S.H., G.D.N., P.F.O., I.M.L., S.E.M. and P.v.d.H. undertook association analysis of individual studies; C.P.N., E.A. and J.R.T. carried out the meta-analysis and the additional reported analyses. H.Z., X.W., D.G. and Y.D. provided data on telomerase activity and genotypes. J.E., M.P.R., S.K. and H.S. contributed CAD association data on behalf of CARDIoGRAM. V.C. and N.J.S. prepared the paper together with C.P.N., E.A., M.M. and P.v.d.H. and all authors reviewed the paper.

Corresponding author

Correspondence toNilesh J Samani.

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The authors declare no competing financial interests.

Additional information

A full list of members is provided in the Supplementary Note.

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Codd, V., Nelson, C., Albrecht, E. et al. Identification of seven loci affecting mean telomere length and their association with disease.Nat Genet 45, 422–427 (2013). https://doi.org/10.1038/ng.2528

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• Received: 26 June 2012
• Accepted: 19 December 2012
• Published: 27 March 2013
• Issue date: April 2013
• DOI: https://doi.org/10.1038/ng.2528