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Genome-wide determinants of mortality and motor progression in Parkinson's disease.
Tan, Manuela M X; Lawton, Michael A; Pollard, Miriam I; Brown, Emmeline; Real, Raquel; Carrasco, Alejandro Martinez; Bekadar, Samir; Jabbari, Edwin; Reynolds, Regina H; Iwaki, Hirotaka; Blauwendraat, Cornelis; Kanavou, Sofia; Hubbard, Leon; Malek, Naveed; Grosset, Katherine A; Bajaj, Nin; Barker, Roger A; Burn, David J; Bresner, Catherine; Foltynie, Thomas; Wood, Nicholas W; Williams-Gray, Caroline H; Andreassen, Ole A; Toft, Mathias; Elbaz, Alexis; Artaud, Fanny; Brice, Alexis; Corvol, Jean-Christophe; Aasly, Jan; Farrer, Matthew J; Nalls, Michael A; Singleton, Andrew B; Williams, Nigel M; Ben-Shlomo, Yoav; Hardy, John; Hu, Michele T M; Grosset, Donald G; Shoai, Maryam; Pihlstrøm, Lasse; Morris, Huw R.
Afiliação
  • Tan MMX; Department of Neurology, Oslo University Hospital, Oslo, Norway. manuela.tan@medisin.uio.no.
  • Lawton MA; Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK. manuela.tan@medisin.uio.no.
  • Pollard MI; UCL Movement Disorders Centre, University College London, London, UK. manuela.tan@medisin.uio.no.
  • Brown E; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Real R; Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
  • Carrasco AM; Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
  • Bekadar S; Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
  • Jabbari E; UCL Movement Disorders Centre, University College London, London, UK.
  • Reynolds RH; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
  • Iwaki H; Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
  • Blauwendraat C; UCL Movement Disorders Centre, University College London, London, UK.
  • Kanavou S; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
  • Hubbard L; Sorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Departement of Neurology, Hôpital Pitié-Salpêtrière, Paris, France.
  • Malek N; Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
  • Grosset KA; UCL Movement Disorders Centre, University College London, London, UK.
  • Bajaj N; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
  • Barker RA; Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Burn DJ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Bresner C; Data Tecnica, Washington DC, USA.
  • Foltynie T; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.
  • Wood NW; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Williams-Gray CH; Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.
  • Andreassen OA; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Toft M; Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
  • Elbaz A; Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
  • Artaud F; Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
  • Brice A; Clinical Neurosciences, University of Nottingham, Nottingham, UK.
  • Corvol JC; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
  • Aasly J; John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Farrer MJ; Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Nalls MA; Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  • Singleton AB; Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
  • Williams NM; Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
  • Ben-Shlomo Y; UCL Movement Disorders Centre, University College London, London, UK.
  • Hardy J; Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
  • Hu MTM; UCL Movement Disorders Centre, University College London, London, UK.
  • Grosset DG; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
  • Shoai M; John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Pihlstrøm L; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Morris HR; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
NPJ Parkinsons Dis ; 10(1): 113, 2024 Jun 07.
Article em En | MEDLINE | ID: mdl-38849413
ABSTRACT
There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci for PD progression. The biology of PD progression is likely to be of central importance in defining mechanisms that can be used to develop new treatments. We studied 6766 PD patients, over 15,340 visits with a mean follow-up of between 4.2 and 15.7 years and carried out genome-wide survival studies for time to a motor progression endpoint, defined by reaching Hoehn and Yahr stage 3 or greater, and death (mortality). There was a robust effect of the APOE ε4 allele on mortality in PD. We also identified a locus within the TBXAS1 gene encoding thromboxane A synthase 1 associated with mortality in PD. We also report 4 independent loci associated with motor progression in or near MORN1, ASNS, PDE5A, and XPO1. Only the non-Gaucher disease causing GBA1 PD risk variant E326K, of the known PD risk variants, was associated with mortality in PD. Further work is needed to understand the links between these genomic variants and the underlying disease biology. However, these may represent new candidates for disease modification in PD.
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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: NPJ Parkinsons Dis Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Noruega
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: NPJ Parkinsons Dis Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Noruega