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Abstract

We conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 individuals, with follow-up replication in 9,492 individuals. We identified an association with telomere length on 3q26 (rs12696304, combined P = 3.72 × 10−14) at a locus that includes TERC, which encodes the telomerase RNA component. Each copy of the minor allele of rs12696304 was associated with an 75-base-pair reduction in mean telomere length, equivalent to 3.6 years of age-related telomere-length attrition.

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Change history

  • 16 April 2010

    Dr. Abraham Aviv and Dr. Masayuki Kimura were inadvertently omitted from the author list and the author contribution statement in the version of the manuscript initially published on February 7, 2010. This has been corrected in the online html and PDF.

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Acknowledgements

The BHF-FHS Study and the GRAPHIC Study were supported by the BHF. The WTCCC and recruitment of the UKBS donors were funded by the Wellcome Trust. The TwinsUK study was funded by the Wellcome Trust and Biotechnology and Biological Sciences Research Council project grant G20234. The PREVEND study is supported by the Dutch Kidney Foundation (grant E033), The Netherlands Heart Foundation (grant 2006B140, 2006T003) and the EU project grant Genomic Strategies for Treatment and Prevention of Cardiovascular Death in Uraemia and End-stage Renal Disease (GENECURE) (FP-6 LSHM CT 2006 037697). We thank J. Marchini for generating the imputed genotypes for the WTCCC cohorts and J. Gardner for generating the telomere length data in the TwinsUK study. V.C., A.H.G. and N.J.S. are supported by the BHF and the Leicester National Institute of Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease. M.M. and T.D.S. are supported by NIHR Biomedical Research Centre award to Guy's & St Thomas' National Health Service Foundation Trust in partnership with King's College London. P.vd.H. is supported by the Netherlands Organisation for Scientific Research (NWO) VENI grant 916.76.170 and the Interuniversity Cardiology Institute of the Netherlands (ICIN). Collaboration between the WTCCC Study telomere GWAS and the TwinsUK study was established under the European Framework 7 (FP7/2007-2013) European Network for Genetic and Genomic Epidemiology (ENGAGE) project (HEALTH-F4-2007- 201413).

Author information

Author notes

    • Veryan Codd
    • , Massimo Mangino
    • , Pim van der Harst
    • , Tim Spector
    •  & Nilesh J Samani

    These authors contributed equally to this work.

Affiliations

  1. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.

    • Veryan Codd
    • , Pim van der Harst
    • , Peter S Braund
    • , Michael Kaiser
    • , Alan J Beveridge
    • , Suzanne Rafelt
    • , Jasbir Moore
    • , Chris Nelson
    • , Alison H Goodall
    •  & Nilesh J Samani
  2. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

    • Massimo Mangino
    • , Nicole Soranzo
    • , Guangju Zhai
    • , Ana M Valdes
    •  & Tim Spector
  3. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Pim van der Harst
    • , Irene Mateo Leach
    • , Rudolf A de Boer
    • , Dirk J van Veldhuisen
    •  & Wiek H van Gilst
  4. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.

    • Nicole Soranzo
    •  & Hannah Blackburn
  5. The Center of Human Development and Aging, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.

    • Masayuki Kimura
    •  & Abraham Aviv
  6. Department of Hematology, University of Cambridge, Cambridge, UK.

    • Willem Ouwehand
  7. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Gerjan Navis
  8. Departments of Health Sciences and Genetics, University of Leicester, Leicester, UK.

    • Paul R Burton
    • , Martin D Tobin
    •  & John R Thompson
  9. Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.

    • Alistair S Hall

Consortia

  1. Wellcome Trust Case Control Consortium

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

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Contributions

N.J.S. and T.S. conceived the study. V.C., M.M. and P.v.d.H. designed the laboratory work and conducted the analyses. V.C., P.S.B., M.Kaiser, J.M., I.M.L. and R.A.d.B. undertook the laboratory work. A.J.B. provided bioinformatics support and S.R., C.N. and N.S. undertook statistical support. A.S.H. and N.J.S. recruited and provided samples and data from the BHF Family Heart Study; W.T.C.C.C. and W.O. from the UKBS samples; A.H.G., P.R.B., M.D.T. and N.J.S. from the GRAPHIC study; G.Z., A.M.V., H.B., M.Kimura, A.A. and T.S. from the TwinsUK study; and D.J.v.V., W.H.v.G. and G.N. from the PREVEND Study. J.R.T. oversaw the statistical analysis. The paper was written by V.C., M.M. and N.J.S. All authors contributed to the final version of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Nilesh J Samani.

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    Supplementary Figure 1, Supplementary Tables 1–5, Supplementary Methods and Supplementary Note

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DOI

https://doi.org/10.1038/ng.532

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