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).
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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.
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A full list of members is provided is provided in the Supplementary Note.
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Codd, V., Mangino, M., van der Harst, P. et al. Common variants near TERC are associated with mean telomere length. Nat Genet 42, 197–199 (2010). https://doi.org/10.1038/ng.532
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DOI: https://doi.org/10.1038/ng.532
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