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dc.contributor.authorJones, Garan
dc.contributor.authorTrajanoska, Katerina
dc.contributor.authorSantanasto, Adam J.
dc.contributor.authorStringa, Najada
dc.contributor.authorKuo, Chia-Ling
dc.contributor.authorAtkins, Janice L.
dc.contributor.authorLewis, Joshua R.
dc.contributor.authorDuong, ThuyVy
dc.contributor.authorHong, Shengjun
dc.contributor.authorBiggs, Mary L.
dc.contributor.authorLuan, Jian’an
dc.contributor.authorSarnowski, Chloe
dc.contributor.authorLunetta, Kathryn L.
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorWojczynski, Mary K.
dc.contributor.authorCvejkus, Ryan
dc.contributor.authorNethander, Maria
dc.contributor.authorGhasemi, Sahar
dc.contributor.authorYang, Jingyun
dc.contributor.authorZillikens, M. Carola
dc.contributor.authorWalter, Stefan
dc.contributor.authorSicinski, Kamil
dc.contributor.authorKague, Erika
dc.contributor.authorAckert-Bicknell, Cheryl L.
dc.contributor.authorArking, Dan E.
dc.contributor.authorWindham, B. Gwen
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorGrove, Megan L.
dc.contributor.authorGraff, Misa
dc.contributor.authorSpira, Dominik
dc.contributor.authorDemuth, Ilja
dc.contributor.authorvan der Velde, Nathalie
dc.contributor.authorde Groot, Lisette C. P. G. M.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorOdden, Michelle C.
dc.contributor.authorFohner, Alison E.
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorWareham, Nicholas J.
dc.contributor.authorBandinelli, Stefania
dc.contributor.authorvan Schoor, Natasja M.
dc.contributor.authorHuisman, Martijn
dc.contributor.authorTan, Qihua
dc.contributor.authorZmuda, Joseph
dc.contributor.authorMellström, Dan
dc.contributor.authorKarlsson, Magnus
dc.contributor.authorBennett, David A.
dc.contributor.authorBuchman, Aron S.
dc.contributor.authorDe Jager, Philip L.
dc.contributor.authorUitterlinden, Andre G.
dc.contributor.authorVölker, Uwe
dc.contributor.authorKocher, Thomas
dc.contributor.authorTeumer, Alexander
dc.contributor.authorRodriguéz-Mañas, Leocadio
dc.contributor.authorGarcía, Francisco J.
dc.contributor.authorCarnicero, José A.
dc.contributor.authorHerd, Pamela
dc.contributor.authorBertram, Lars
dc.contributor.authorOhlsson, Claes
dc.contributor.authorMurabito, Joanne M.
dc.contributor.authorMelzer, David
dc.contributor.authorKuchel, George A.
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorKarasik, David
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorKiel, Douglas P.
dc.contributor.authorPilling, Luke C.
dc.date.accessioned2021-01-28T16:15:15Z
dc.date.available2021-01-28T16:15:15Z
dc.date.issued2021-01-28
dc.date.submitted2020-05-13
dc.identifier.others41467-021-20918-w
dc.identifier.other20918
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316826
dc.description.abstractAbstract: Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p = 4 × 10−17), arthritis (GDF5p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/208/205
dc.subject/631/208/212
dc.subject/692/53/2423
dc.subject/692/308/2056
dc.subject/45
dc.subject/45/43
dc.subjectarticle
dc.titleGenome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
dc.typeArticle
dc.date.updated2021-01-28T16:15:15Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume12
dc.identifier.doi10.17863/CAM.63941
dcterms.dateAccepted2020-12-22
rioxxterms.versionofrecord10.1038/s41467-021-20918-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidJones, Garan [0000-0002-8917-3930]
dc.contributor.orcidTrajanoska, Katerina [0000-0002-3792-4296]
dc.contributor.orcidSantanasto, Adam J. [0000-0002-6912-2909]
dc.contributor.orcidStringa, Najada [0000-0001-6350-452X]
dc.contributor.orcidAtkins, Janice L. [0000-0003-4919-9068]
dc.contributor.orcidLewis, Joshua R. [0000-0003-1003-8443]
dc.contributor.orcidLuan, Jian’an [0000-0003-3137-6337]
dc.contributor.orcidSarnowski, Chloe [0000-0002-6090-7099]
dc.contributor.orcidLunetta, Kathryn L. [0000-0002-9268-810X]
dc.contributor.orcidCvejkus, Ryan [0000-0001-5287-5341]
dc.contributor.orcidNethander, Maria [0000-0003-3688-906X]
dc.contributor.orcidYang, Jingyun [0000-0002-3495-3710]
dc.contributor.orcidWalter, Stefan [0000-0002-6010-7550]
dc.contributor.orcidKague, Erika [0000-0002-0266-9424]
dc.contributor.orcidGraff, Misa [0000-0001-6380-1735]
dc.contributor.orcidde Groot, Lisette C. P. G. M. [0000-0003-2778-2789]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidWareham, Nicholas J. [0000-0003-1422-2993]
dc.contributor.orcidTan, Qihua [0000-0003-3194-0030]
dc.contributor.orcidBuchman, Aron S. [0000-0002-6426-2742]
dc.contributor.orcidDe Jager, Philip L. [0000-0002-8057-2505]
dc.contributor.orcidUitterlinden, Andre G. [0000-0002-7276-3387]
dc.contributor.orcidVölker, Uwe [0000-0002-5689-3448]
dc.contributor.orcidKocher, Thomas [0000-0001-9605-2822]
dc.contributor.orcidTeumer, Alexander [0000-0002-8309-094X]
dc.contributor.orcidBertram, Lars [0000-0002-0108-124X]
dc.contributor.orcidMelzer, David [0000-0002-0170-3838]
dc.contributor.orcidKuchel, George A. [0000-0001-8387-7040]
dc.contributor.orcidFerrucci, Luigi [0000-0002-6273-1613]
dc.contributor.orcidKarasik, David [0000-0002-8826-0530]
dc.contributor.orcidRivadeneira, Fernando [0000-0001-9435-9441]
dc.contributor.orcidKiel, Douglas P. [0000-0001-8474-0310]
dc.contributor.orcidPilling, Luke C. [0000-0002-3332-8454]
dc.identifier.eissn2041-1723
pubs.funder-project-idRCUK | Medical Research Council (MRC) (MR/M023095/1)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)