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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.

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dc.contributor.authorLi, Chen
dc.contributor.authorStoma, Svetlana
dc.contributor.authorLotta, Luca A
dc.contributor.authorWarner, Sophie
dc.contributor.authorAlbrecht, Eva
dc.contributor.authorAllione, Alessandra
dc.contributor.authorArp, Pascal P
dc.contributor.authorBroer, Linda
dc.contributor.authorBuxton, Jessica L
dc.contributor.authorDa Silva Couto Alves, Alexessander
dc.contributor.authorDeelen, Joris
dc.contributor.authorFedko, Iryna O
dc.contributor.authorGordon, Scott D
dc.contributor.authorJiang, Tao
dc.contributor.authorKarlsson, Robert
dc.contributor.authorKerrison, Nicola
dc.contributor.authorLoe, Taylor K
dc.contributor.authorMangino, Massimo
dc.contributor.authorMilaneschi, Yuri
dc.contributor.authorMiraglio, Benjamin
dc.contributor.authorPervjakova, Natalia
dc.contributor.authorRusso, Alessia
dc.contributor.authorSurakka, Ida
dc.contributor.authorvan der Spek, Ashley
dc.contributor.authorVerhoeven, Josine E
dc.contributor.authorAmin, Najaf
dc.contributor.authorBeekman, Marian
dc.contributor.authorBlakemore, Alexandra I
dc.contributor.authorCanzian, Federico
dc.contributor.authorHamby, Stephen E
dc.contributor.authorHottenga, Jouke-Jan
dc.contributor.authorJones, Peter D
dc.contributor.authorJousilahti, Pekka
dc.contributor.authorMägi, Reedik
dc.contributor.authorMedland, Sarah E
dc.contributor.authorMontgomery, Grant W
dc.contributor.authorNyholt, Dale R
dc.contributor.authorPerola, Markus
dc.contributor.authorPietiläinen, Kirsi H
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorSillanpää, Elina
dc.contributor.authorSuchiman, H Eka
dc.contributor.authorvan Heemst, Diana
dc.contributor.authorWillemsen, Gonneke
dc.contributor.authorAgudo, Antonio
dc.contributor.authorBoeing, Heiner
dc.contributor.authorBoomsma, Dorret I
dc.contributor.authorChirlaque, Maria-Dolores
dc.contributor.authorFagherazzi, Guy
dc.contributor.authorFerrari, Pietro
dc.contributor.authorFranks, Paul
dc.contributor.authorGieger, Christian
dc.contributor.authorEriksson, Johan Gunnar
dc.contributor.authorGunter, Marc
dc.contributor.authorHägg, Sara
dc.contributor.authorHovatta, Iiris
dc.contributor.authorImaz, Liher
dc.contributor.authorKaprio, Jaakko
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorKey, Timothy
dc.contributor.authorKrogh, Vittorio
dc.contributor.authorMartin, Nicholas G
dc.contributor.authorMelander, Olle
dc.contributor.authorMetspalu, Andres
dc.contributor.authorMoreno, Concha
dc.contributor.authorOnland-Moret, N Charlotte
dc.contributor.authorNilsson, Peter
dc.contributor.authorOng, Ken K
dc.contributor.authorOvervad, Kim
dc.contributor.authorPalli, Domenico
dc.contributor.authorPanico, Salvatore
dc.contributor.authorPedersen, Nancy L
dc.contributor.authorPenninx, Brenda W J H
dc.contributor.authorQuiros, J Ramon
dc.contributor.authorJarvelin, Marjo Riitta
dc.contributor.authorRodriguez-Barranco, Miguel
dc.contributor.authorScott, Robert A
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorSlagboom, P Eline
dc.contributor.authorSpector, Tim D
dc.contributor.authorTjonneland, Anne
dc.contributor.authorTrichopoulou, Antonia
dc.contributor.authorTumino, Rosario
dc.contributor.authorUitterlinden, André G
dc.contributor.authorvan der Schouw, Yvonne T
dc.contributor.authorvan Duijn, Cornelia M
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorDenchi, Eros Lazzerini
dc.contributor.authorMatullo, Giuseppe
dc.contributor.authorButterworth, Adam S
dc.contributor.authorDanesh, John
dc.contributor.authorSamani, Nilesh J
dc.contributor.authorWareham, Nicholas J
dc.contributor.authorNelson, Christopher P
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorCodd, Veryan
dc.contributor.funderEuropean Union Framework 7—Health Theme
dc.contributor.funderEuropean Union
dc.contributor.funderUK Medical Research Council
dc.contributor.funderBritish Heart Foundation
dc.contributor.funderEuropean Commission Framework Programme 7
dc.date.accessioned2023-02-08T14:42:19Z
dc.date.available2023-02-08T14:42:19Z
dc.date.issued2020-02-10
dc.description.abstractLeukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) 350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
dc.description.sponsorshipThe ENGAGE Project was funded under the European Union Framework 7—Health Theme (HEALTH-F4-2007- 201413). The InterAct project received funding from the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Programme 6 of the European Community). The EPIC-CVD study was supported by core funding from the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/ 13/30194; RG/18/13/33946), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals National Health Service (NHS) Foundation Trust)[*]. C.P.N is funded by the British Heart Foundation (BHF). V.C., C.P.N., and N.J.S. are supported by the National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Centre and N.J.S. holds an NIHR Senior Investigator award. Chen Li is support by a four-year Wellcome Trust PhD Studentship; C.L., L.A.L., and N.J.W. are funded by the Medical Research Council (MC_UU_12015/1). N.J.W. is an NIHR Senior Investigator. J.D. is funded by the NIHR (Senior Investigator Award).[*]. *The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Cohort-specific and further acknowledgments are given in the Supplemental Information.
dc.description.versionSi
dc.identifier.citationLi C, Stoma S, Lotta LA, Warner S, Albrecht E, Allione A, et al. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length. Am J Hum Genet. 2020 Mar 5;106(3):389-404.
dc.identifier.doi10.1016/j.ajhg.2020.02.006
dc.identifier.essn1537-6605
dc.identifier.pmcPMC7058826
dc.identifier.pmid32109421
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058826/pdf
dc.identifier.unpaywallURLhttp://www.cell.com/article/S0002929720300483/pdf
dc.identifier.urihttp://hdl.handle.net/10668/15179
dc.issue.number3
dc.journal.titleAmerican journal of human genetics
dc.journal.titleabbreviationAm J Hum Genet
dc.language.isoen
dc.organizationEscuela Andaluza de Salud Pública-EASP
dc.organizationInstituto de Investigación Biosanitaria de Granada (ibs.GRANADA)
dc.page.number389-404
dc.publisherCell Press
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDHEALTH-F4-2007- 201413
dc.relation.projectIDLSHM-CT-2006-037197
dc.relation.projectIDMR/L003120/1
dc.relation.projectIDRG/13/13/30194
dc.relation.projectIDRG/18/13/33946
dc.relation.projectIDHEALTH-F2-2012-279233
dc.relation.projectIDMC_UU_12015/1
dc.relation.publisherversionhttps://linkinghub.elsevier.com/retrieve/pii/S0002-9297(20)30048-3
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMendelian randomisation
dc.subjectage-related disease
dc.subjectbiological aging
dc.subjecttelomere length
dc.subject.decsTelómero
dc.subject.decsNucleótidos
dc.subject.decsLeucocitos
dc.subject.decsHumanos
dc.subject.decsEstudio de asociación del genoma completo
dc.subject.meshGenome-Wide Association Study
dc.subject.meshHumans
dc.subject.meshLeukocytes
dc.subject.meshNucleotides
dc.subject.meshTelomere
dc.titleGenome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number106
dspace.entity.typePublication

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