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dc.contributor.authorIwaki, Hirotakaen
dc.contributor.authorBlauwendraat, Cornelisen
dc.contributor.authorLeonard, Hampton Len
dc.contributor.authorLiu, Ganqiangen
dc.contributor.authorMaple-Grødem, Jodien
dc.contributor.authorCorvol, Jean-Christopheen
dc.contributor.authorPihlstrøm, Lasseen
dc.contributor.authorvan Nimwegen, Marliesen
dc.contributor.authorHutten, Samantha Jen
dc.contributor.authorNguyen, Khanh-Dung Hen
dc.contributor.authorRick, Jacquelineen
dc.contributor.authorEberly, Shirleyen
dc.contributor.authorFaghri, Farazen
dc.contributor.authorAuinger, Peggyen
dc.contributor.authorScott, Kirsten Men
dc.contributor.authorWijeyekoon, Ruwanien
dc.contributor.authorVan Deerlin, Vivianna Men
dc.contributor.authorHernandez, Dena Gen
dc.contributor.authorDay-Williams, Aaron Gen
dc.contributor.authorBrice, Alexisen
dc.contributor.authorAlves, Guidoen
dc.contributor.authorNoyce, Alastair Jen
dc.contributor.authorTysnes, Ole-Bjørnen
dc.contributor.authorEvans, Jonathan Ren
dc.contributor.authorBreen, David Pen
dc.contributor.authorEstrada, Karolen
dc.contributor.authorWegel, Claire Een
dc.contributor.authorDanjou, Fabriceen
dc.contributor.authorSimon, David Ken
dc.contributor.authorRavina, Bernarden
dc.contributor.authorToft, Mathiasen
dc.contributor.authorHeutink, Peteren
dc.contributor.authorBloem, Bastiaan Ren
dc.contributor.authorWeintraub, Danielen
dc.contributor.authorBarker, Rogeren
dc.contributor.authorWilliams-Gray, Carolineen
dc.contributor.authorvan de Warrenburg, Bart Pen
dc.contributor.authorVan Hilten, Jacobus Jen
dc.contributor.authorScherzer, Clemens Ren
dc.contributor.authorSingleton, Andrew Ben
dc.contributor.authorNalls, Mike Aen
dc.date.accessioned2019-05-03T23:32:24Z
dc.date.available2019-05-03T23:32:24Z
dc.date.issued2019-08en
dc.identifier.issn2376-7839
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/292405
dc.description.abstractObjective To determine if any association between previously identified alleles that confer risk for Parkinson’s disease and variables measuring disease progression. Methods We evaluated the association between 31 risk variants and variables measuring disease progression. A total of 23,423 visits by 4,307 patients of European ancestry from 13 longitudinal cohorts in Europe, North America, and Australia were analyzed Results We confirmed the importance of GBA on phenotypes. GBA variants were associated with the development of daytime sleepiness (p.N370S: HR 3.28 [1.69, 6.34]) and possible REM sleep behavior (p.T408M: OR 6.48 [2.04, 20.60]). We also replicated previously reported associations of GBA variants with motor/cognitive declines. The other genotype-phenotype associations include an intergenic variant near LRRK2 and the faster development of motor symptom (Hoehn and Yahr scale 3.0 HR 1.33 [1.16, 1.52] for the C allele of rs76904798); an intronic variant in PMVK and the development of wearing-off effects (HR 1.66 [1.19, 2.31] for the C allele of rs114138760).Age of onset was associated with TMEM175 variant p.M393T (-0.72 [-1.21, -0.23] in years), the C allele of rs199347 (intronic region of GPNMB, 0.70 [0.27, 1.14]), and G allele of rs1106180 (intronic region of CCDC62, 0.62 [0.21, 1.03]) Conclusions This study provides evidence that alleles associated with Parkinson’s disease risk, in particular GBA variants, also contribute to the heterogeneity of multiple motor and non-motor aspects. Accounting for genetic variability will be a useful factor in understanding disease course and in minimizing heterogeneity in clinical trials.
dc.description.sponsorshipThe Intramural Research Program the National Institute on Aging (NIA, Z01-AG000949-02), Biogen Idec, and the Michael J Fox Foundation for Parkinson’s Research
dc.format.mediumElectronic-eCollectionen
dc.languageengen
dc.rightsAll rights reserved
dc.titleGenetic risk of Parkinson disease and progression:: An analysis of 13 longitudinal cohorts.en
dc.typeArticle
prism.issueIdentifier4en
prism.publicationDate2019en
prism.publicationNameNeurology. Geneticsen
prism.startingPagee348
prism.volume5en
dc.identifier.doi10.17863/CAM.39555
dcterms.dateAccepted2019-04-30en
rioxxterms.versionofrecord10.1212/nxg.0000000000000348en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-08en
dc.contributor.orcidLeonard, Hampton L [0000-0003-2390-8110]
dc.contributor.orcidMaple-Grødem, Jodi [0000-0001-7142-0078]
dc.contributor.orcidCorvol, Jean-Christophe [0000-0001-7325-0199]
dc.contributor.orcidPihlstrøm, Lasse [0000-0002-7635-8645]
dc.contributor.orcidFaghri, Faraz [0000-0001-5744-8728]
dc.contributor.orcidBrice, Alexis [0000-0002-0941-3990]
dc.contributor.orcidAlves, Guido [0000-0003-0630-2870]
dc.contributor.orcidDanjou, Fabrice [0000-0002-4976-2327]
dc.contributor.orcidHeutink, Peter [0000-0001-5218-1737]
dc.contributor.orcidBarker, Roger [0000-0001-8843-7730]
dc.contributor.orcidWilliams-Gray, Caroline [0000-0002-2648-9743]
dc.contributor.orcidScherzer, Clemens R [0000-0002-0567-9193]
dc.identifier.eissn2376-7839
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
cam.orpheus.successMon Jun 08 08:23:46 BST 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2022-05-03


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