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Polygenic basis and biomedical consequences of telomere length variation

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dc.contributor.authorCodd, Veryan
dc.contributor.authorWang, Qingning
dc.contributor.authorAllara, Elias
dc.contributor.authorMusicha, Crispin
dc.contributor.authorKaptoge, Stephen
dc.contributor.authorStoma, Svetlana
dc.contributor.authorJiang, Tao
dc.contributor.authorHamby, Stephen E.
dc.contributor.authorBraund, Peter S.
dc.contributor.authorBountziouka, Vasiliki
dc.contributor.authorBudgeon, Charley A.
dc.contributor.authorDenniff, Matthew
dc.contributor.authorSwinfield, Chloe
dc.contributor.authorPapakonstantinou, Manolo
dc.contributor.authorSheth, Shilpi
dc.contributor.authorNanus, Dominika E.
dc.contributor.authorWarner, Sophie C.
dc.contributor.authorWang, Minxian
dc.contributor.authorKhera, Amit V.
dc.contributor.authorEales, James
dc.contributor.authorOuwehand, Willem H.
dc.contributor.authorThompson, John R.
dc.contributor.authorDi Angelantonio, Emanuele
dc.contributor.authorWood, Angela M.
dc.contributor.authorButterworth, Adam S.
dc.contributor.authorDanesh, John N.
dc.contributor.authorNelson, Christopher P.
dc.contributor.authorSamani, Nilesh J.
dc.contributor.orcidCodd, Veryan [0000-0002-9430-8254]
dc.contributor.orcidAllara, Elias [0000-0002-1634-8330]
dc.contributor.orcidBraund, Peter S. [0000-0001-8540-5709]
dc.contributor.orcidPapakonstantinou, Manolo [0000-0003-2664-9046]
dc.contributor.orcidWang, Minxian [0000-0002-3753-508X]
dc.contributor.orcidKhera, Amit V. [0000-0001-6535-5839]
dc.contributor.orcidEales, James [0000-0001-6238-5952]
dc.contributor.orcidOuwehand, Willem H. [0000-0002-7744-1790]
dc.contributor.orcidThompson, John R. [0000-0003-4819-1611]
dc.contributor.orcidButterworth, Adam S. [0000-0002-6915-9015]
dc.contributor.orcidSamani, Nilesh J. [0000-0002-3286-8133]
dc.date.accessioned2021-10-06T15:47:04Z
dc.date.available2021-10-06T15:47:04Z
dc.date.issued2021-10-05
dc.date.submitted2021-03-21
dc.date.updated2021-10-06T15:47:02Z
dc.descriptionFunder: Health Data Research UK EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart (11607).
dc.descriptionFunder: Health Data Research UK
dc.description.abstractAbstract: Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.
dc.identifier.doi10.17863/CAM.76492
dc.identifier.eissn1546-1718
dc.identifier.issn1061-4036
dc.identifier.others41588-021-00944-6
dc.identifier.other944
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329047
dc.languageen
dc.publisherNature Publishing Group US
dc.subjectArticle
dc.subject/631/208/205/2138
dc.subject/692/308/2056
dc.subject/45/43
dc.subjectarticle
dc.titlePolygenic basis and biomedical consequences of telomere length variation
dc.typeArticle
dcterms.dateAccepted2021-08-18
prism.endingPage1433
prism.issueIdentifier10
prism.publicationNameNature Genetics
prism.startingPage1425
prism.volume53
pubs.funder-project-idRCUK | Medical Research Council (MRC) (MR/M012816/1, MR/M012816/1, MR/M012816/1, MR/L003120/1, MR/L003120/1, R/L003120/1, MR/M012816/1, MR/M012816/1, MR/M012816/1, MR/M012816/1, MR/M012816/1, MR/M012816/1, MR/L003120/1, MR/L003120/1, MR/L003120/1, MR/M012816/1)
pubs.funder-project-idDH | National Institute for Health Research (NIHR) (BRC-1215-20010, BRC-1215-20010, BRC-1215-20010, BRC-1215-20014, NIHR BTRU-2014-10024, BRC-1215-20010, BRC-1215-20014, NIHR BTRU-2014-10024, BRC-1215-20014, NIHR BTRU-2014-10024, BRC-1215-20010, BRC-1215-20010, BRC-1215-20010, BRC-1215-20014, NIHR BTRU-2014-10024, BRC-1215-20014, NIHR BTRU-2014-10024, BRC-1215-20014, NIHR BTRU-2014-10024, BRC-1215-20014, NIHR BTRU-2014-10024, BRC-1215-20010)
pubs.funder-project-idBritish Heart Foundation (BHF) (RG/13/13/30194, RG/18/13/33946, RG/13/13/30194, RG/18/13/33946, RG/13/13/30194, RG/18/13/33946, SP/16/4/32697, RG/13/13/30194, RG/13/13/30194, RG/18/13/33946, RG/13/13/30194, RG/18/13/33946, RG/13/13/30194, RG/18/13/33946, SP/16/4/32697)
pubs.funder-project-idBHF Centre of Research Excellence, Oxford (BHF Centre of Research Excellence in Oxford) (RG/18/13/33946)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41588-021-00944-6

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