Vis enkel innførsel

dc.contributor.authorIwaki, Hirotakaen_US
dc.contributor.authorBlauwendraat, Cornelisen_US
dc.contributor.authorLeonard, Hampton L.en_US
dc.contributor.authorLiu, Ganqiangen_US
dc.contributor.authorMaple-Grødem, Jodien_US
dc.contributor.authorCorvol, Jean-Christopheen_US
dc.contributor.authorPihlstrøm, Lasseen_US
dc.contributor.authorvan Nimwegen, Marliesen_US
dc.contributor.authorHutten, Samantha J.en_US
dc.contributor.authorNguyen, Khanh-Dung H.en_US
dc.contributor.authorRick, Jacquelineen_US
dc.contributor.authorEberly, Shirleyen_US
dc.contributor.authorFaghri, Farazen_US
dc.contributor.authorAuinger, Peggyen_US
dc.contributor.authorScott, Kirsten M.en_US
dc.contributor.authorWijeyekoon, Ruwanien_US
dc.contributor.authorvan Deerlin, Vivianna M.en_US
dc.contributor.authorHernandez, Dena G.en_US
dc.contributor.authorDay-Williams, Aaron G.en_US
dc.contributor.authorBrice, Alexisen_US
dc.contributor.authorAlves, Guido Werneren_US
dc.contributor.authorNoyce, Alastair J.en_US
dc.contributor.authorTysnes, Ole-Bjørnen_US
dc.contributor.authorEvans, Jonathan R.en_US
dc.contributor.authorBreen, David P.en_US
dc.contributor.authorEstrada, Karolen_US
dc.contributor.authorWegel, Claire E.en_US
dc.contributor.authorDanjou, Fabriceen_US
dc.contributor.authorSimon, David K.en_US
dc.contributor.authorRavina, Bernarden_US
dc.contributor.authorToft, Mathiasen_US
dc.contributor.authorHeutink, Peteren_US
dc.contributor.authorBloem, Bastiaan R.en_US
dc.contributor.authorWeintraub, Danielen_US
dc.contributor.authorBarker, Roger A.en_US
dc.contributor.authorWilliams-Gray, Caroline H.en_US
dc.contributor.authorvan de Warrenburg, Bart P.en_US
dc.contributor.authorvan Hilten, Jacobus J.en_US
dc.contributor.authorScherzer, Clemens R.en_US
dc.contributor.authorSingleton, Andrew B.en_US
dc.contributor.authorNalls, Mike A.en_US
dc.date.accessioned2020-08-07T07:21:02Z
dc.date.available2020-08-07T07:21:02Z
dc.date.issued2019
dc.PublishedIwaki H, Blauwendraat C, Leonard HL, Liu G, Maple-Grødem J, Corvol J, et al. Genetic risk of Parkinson disease and progression: An analysis of 13 longitudinal cohorts. Neurology: Genetics. 2019;5(4):e348eng
dc.identifier.issn2376-7839
dc.identifier.urihttps://hdl.handle.net/1956/23539
dc.description.abstractObjective: To determine if any association between previously identified alleles that confer risk for Parkinson 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: hazard ratio [HR] 3.28 [1.69–6.34]) and possible REM sleep behavior (p.T408M: odds ratio 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) and 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 at onset was associated with TMEM175 variant p.M393T (−0.72 [−1.21 to −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 disease risk, in particular GBA variants, also contribute to the heterogeneity of multiple motor and nonmotor aspects. Accounting for genetic variability will be a useful factor in understanding disease course and in minimizing heterogeneity in clinical trials.en_US
dc.language.isoengeng
dc.publisherWolters Kluwereng
dc.rightsAttribution-Non Commercial-No Derivatives CC BY-NC-NDeng
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/eng
dc.titleGenetic risk of Parkinson disease and progression: An analysis of 13 longitudinal cohortsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2020-02-11T15:26:23Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2019 The Authors
dc.identifier.doihttps://doi.org/10.1212/nxg.0000000000000348
dc.identifier.cristin1748394
dc.source.journalNeurology: Genetics


Tilhørende fil(er)

Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel

Attribution-Non Commercial-No Derivatives CC BY-NC-ND
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution-Non Commercial-No Derivatives CC BY-NC-ND