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Genomewide association study of Parkinson's disease clinical biomarkers in 12 longitudinal patients' cohorts.
Iwaki, Hirotaka; Blauwendraat, Cornelis; Leonard, Hampton L; Kim, Jonggeol J; Liu, Ganqiang; Maple-Grødem, Jodi; Corvol, Jean-Christophe; Pihlstrøm, Lasse; van Nimwegen, Marlies; Hutten, Samantha J; Nguyen, Khanh-Dung H; Rick, Jacqueline; Eberly, Shirley; Faghri, Faraz; Auinger, Peggy; Scott, Kirsten M; Wijeyekoon, Ruwani; Van Deerlin, Vivianna M; Hernandez, Dena G; Gibbs, J Raphael; Chitrala, Kumaraswamy Naidu; Day-Williams, Aaron G; Brice, Alexis; Alves, Guido; Noyce, Alastair J; Tysnes, Ole-Bjørn; Evans, Jonathan R; Breen, David P; Estrada, Karol; Wegel, Claire E; Danjou, Fabrice; Simon, David K; Andreassen, Ole; Ravina, Bernard; Toft, Mathias; Heutink, Peter; Bloem, Bastiaan R; Weintraub, Daniel; Barker, Roger A; Williams-Gray, Caroline H; van de Warrenburg, Bart P; Van Hilten, Jacobus J; Scherzer, Clemens R; Singleton, Andrew B; Nalls, Mike A.
Afiliación
  • Iwaki H; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
  • Blauwendraat C; Data Tecnica International, Glen Echo, Maryland, USA.
  • Leonard HL; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
  • Kim JJ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
  • Liu G; Data Tecnica International, Glen Echo, Maryland, USA.
  • Maple-Grødem J; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
  • Corvol JC; School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • Pihlstrøm L; Advanced Center for Parkinson's Disease Research, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • van Nimwegen M; Precision Neurology Program, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Hutten SJ; The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.
  • Nguyen KH; Department of Chemistry, Bioscience and Environmental Engineering, University in Stavanger, Stavanger, Norway.
  • Rick J; Assistance-Publique Hôpitaux de Paris, ICM, INSERM UMRS 1127, CNRS 7225, ICM, Department of Neurology and CIC Neurosciences, Pitié-Salpêtrière Hospital, Paris, France.
  • Eberly S; Department of Neurology, Oslo University Hospital, Oslo, Norway.
  • Faghri F; Radboud University Medical Centre, Donders Institute for Brain, Cognition, and Behaviour; Department of Neurology, Nijmegen, The Netherlands.
  • Auinger P; The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
  • Scott KM; Translational Genome Sciences, Biogen, Cambridge, Massachusetts, USA.
  • Wijeyekoon R; Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Van Deerlin VM; Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, USA.
  • Hernandez DG; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
  • Gibbs JR; Department of Computer Science, University of Illinois Urbana-Champaign, Champaign, Illinois, USA.
  • Chitrala KN; Department of Clinical Neurosciences, University of Cambridge, John van Geest Centre for Brain Repair, Cambridge, United Kingdom.
  • Day-Williams AG; Department of Clinical Neurosciences, University of Cambridge, John van Geest Centre for Brain Repair, Cambridge, United Kingdom.
  • Brice A; Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Parelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Alves G; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
  • Noyce AJ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
  • Evans JR; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
  • Breen DP; Flagship Labs 60 Inc, Cambridge, Massachusetts, USA.
  • Estrada K; Statistical Genetics, Biogen, Cambridge, Massachusetts, USA.
  • Wegel CE; Institut du cerveau et de la moelle épinière ICM, Paris, France.
  • Danjou F; Sorbonne Université SU, Paris, France.
  • Simon DK; INSERM UMR1127, Paris, France.
  • Andreassen O; The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.
  • Ravina B; Department of Chemistry, Bioscience and Environmental Engineering, University in Stavanger, Stavanger, Norway.
  • Toft M; Department of Neurology, Stavanger University Hospital, Stavanger, Norway.
  • Heutink P; Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
  • Bloem BR; Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, United Kingdom.
  • Weintraub D; Department of Neurology, Haukeland University Hospital, Bergen, Norway.
  • Barker RA; University of Bergen, Bergen, Norway.
  • Williams-Gray CH; Department of Neurology, Nottingham University NHS Trust, Nottingham, United Kingdom.
  • van de Warrenburg BP; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland.
  • Van Hilten JJ; Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, Scotland.
  • Scherzer CR; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
  • Singleton AB; Translational Genome Sciences, Biogen, Cambridge, Massachusetts, USA.
  • Nalls MA; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA.
Mov Disord ; 34(12): 1839-1850, 2019 12.
Article en En | MEDLINE | ID: mdl-31505070
ABSTRACT

BACKGROUND:

Several reports have identified different patterns of Parkinson's disease progression in individuals carrying missense variants in GBA or LRRK2 genes. The overall contribution of genetic factors to the severity and progression of Parkinson's disease, however, has not been well studied.

OBJECTIVES:

To test the association between genetic variants and the clinical features of Parkinson's disease on a genomewide scale.

METHODS:

We accumulated individual data from 12 longitudinal cohorts in a total of 4093 patients with 22,307 observations for a median of 3.81 years. Genomewide associations were evaluated for 25 cross-sectional and longitudinal phenotypes. Specific variants of interest, including 90 recently identified disease-risk variants, were also investigated post hoc for candidate associations with these phenotypes.

RESULTS:

Two variants were genomewide significant. Rs382940(T>A), within the intron of SLC44A1, was associated with reaching Hoehn and Yahr stage 3 or higher faster (hazard ratio 2.04 [1.58-2.62]; P value = 3.46E-8). Rs61863020(G>A), an intergenic variant and expression quantitative trait loci for α-2A adrenergic receptor, was associated with a lower prevalence of insomnia at baseline (odds ratio 0.63 [0.52-0.75]; P value = 4.74E-8). In the targeted analysis, we found 9 associations between known Parkinson's risk variants and more severe motor/cognitive symptoms. Also, we replicated previous reports of GBA coding variants (rs2230288 p.E365K; rs75548401 p.T408M) being associated with greater motor and cognitive decline over time, and an APOE E4 tagging variant (rs429358) being associated with greater cognitive deficits in patients.

CONCLUSIONS:

We identified novel genetic factors associated with heterogeneity of Parkinson's disease. The results can be used for validation or hypothesis tests regarding Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Mov Disord Asunto de la revista: NEUROLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Mov Disord Asunto de la revista: NEUROLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos