Investigation of the genetic aetiology of Lewy body diseases with and without dementia.

APOE Lewy body diseases dementia genome-wide association studies

Journal

Brain communications
ISSN: 2632-1297
Titre abrégé: Brain Commun
Pays: England
ID NLM: 101755125

Informations de publication

Date de publication:
2024
Historique:
received: 20 10 2023
revised: 09 04 2024
accepted: 30 05 2024
medline: 9 7 2024
pubmed: 9 7 2024
entrez: 9 7 2024
Statut: epublish

Résumé

Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson's disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson's disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson's disease and dementia with Lewy bodies/Parkinson's disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson's, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson's Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging

Identifiants

DOI: 10.1093/braincomms/fcae190 PMID: 38978726 PMC: PMC11228432
pubmed: 38978726
doi: 10.1093/braincomms/fcae190
pii: fcae190
pmc: PMC11228432
doi:

Types de publication

Journal Article

Langues

eng

Pagination

fcae190

Investigateurs

Yevgeniya Abramzon (Y)
Sarah Ahmed (S)
Camille Alba (C)
Marilyn S Albert (MS)
Dagmar Bacikova (D)
Matthew J Barrett (MJ)
Thomas G Beach (TG)
David A Bennett (DA)
Lilah M Besser (LM)
Eileen H Bigio (EH)
Bradley F Boeve (BF)
Ryan C Bohannan (RC)
Chad A Caraway (CA)
Jose-Alberto Palma (JA)
Ruth Chia (R)
Clifton L Dalgard (CL)
Dennis Dickson (D)
Jinhui Ding (J)
Kelley Faber (K)
Tanis Ferman (T)
Luigi Ferrucci (L)
Margaret E Flanagan (ME)
Tatiana M Foroud (TM)
Bernardino Ghetti (B)
J Raphael Gibbs (JR)
Alison Goate (A)
David Goldstein (D)
Neill R Graff-Radford (NR)
Heng-Chen Hu (HC)
Daniel Hupalo (D)
Scott M Kaiser (SM)
Horacio Kaufmann (H)
Ronald C Kim (RC)
Gregory Klein (G)
Walter Kukull (W)
Amanda Kuzma (A)
James Leverenz (J)
Grisel Lopez (G)
Qinwen Mao (Q)
Elisa Martinez-McGrath (E)
Eliezer Masliah (E)
Ed Monuki (E)
Kathy L Newell (KL)
Lucy Norcliffe-Kaufmann (L)
Matthew Perkins (M)
Olga Pletnikova (O)
Alan E Renton (AE)
Susan M Resnick (SM)
Owen A Ross (OA)
Marya S Sabir (MS)
Clemens R Scherzer (CR)
Sonja W Scholz (SW)
Geidy Serrano (G)
Vikram Shakkotai (V)
Ellen Sidransky (E)
Andrew B Singleton (AB)
Toshiko Tanaka (T)
Nahid Tayebi (N)
Bryan J Traynor (BJ)
Juan C Troncoso (JC)
Coralie Viollet (C)
Ronald L Walton (RL)
Randy Woltjer (R)
Zbigniew K Wszolek (ZK)
Sandra E Black (SE)
Ziv Gan-Or (Z)
Julia Keith (J)
Mario Masellis (M)
Ekaterina Rogaeva (E)
Dag Aarsland (D)
Safa Al-Sarraj (S)
Johannes Attems (J)
Raffaele Ferrari (R)
Steve Gentleman (S)
John A Hardy (JA)
Angela K Hodges (AK)
Seth Love (S)
Ian McKeith (I)
Christopher M Morris (CM)
Huw R Morris (HR)
Laura Palmer (L)
Stuart Pickering-Brown (S)
Regina H Reynolds (RH)
Mina Ryten (M)
Alan J Thomas (AJ)
Bension S Tilley (BS)
Claire Troakes (C)
Francesca Brett (F)
Alexis Brice (A)
Charles Duyckaerts (C)
Suzanne Lesage (S)
Maura Brunetti (M)
Andrea Calvo (A)
Antonio Canosa (A)
Adriano Chiò (A)
Gianluca Floris (G)
Giancarlo Logroscino (G)
Chiara Zecca (C)
Jordi Clarimon (J)
Monica Diez-Fairen (M)
Juan Fortea (J)
Isabel González-Aramburu (I)
Jon Infante (J)
Carmen Lage (C)
Alberto Lleó (A)
Pau Pastor (P)
Laura Porcel-Molina (L)
Eloy Rodríguez-Rodríguez (E)
Pascual Sanchez-Juan (P)
Rejko Krüger (R)
Patrick May (P)
Georgia Xiromerisiou (G)

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.

Déclaration de conflit d'intérêts

H.R.M. is employed by UCL. In the last 12 months, he reports paid consultancy from Roche, Aprinoia, AI Therapeutics and Amylyx; lecture fees/honoraria from BMJ, Kyowa Kirin and Movement Disorders Society; and research grants from Parkinson's UK, Cure Parkinson's Trust, PSP Association, Medical Research Council and Michael J. Fox Foundation. H.R.M. is a co-applicant on a patent application related to C9ORF72—Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140).

Auteurs

Lesley Yue Wu (LY)

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
UCL Movement Disorders Centre, University College London, London WC1N 3BG, UK.
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
ORCID: 0000-0001-5464-5603

Raquel Real (R)

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
UCL Movement Disorders Centre, University College London, London WC1N 3BG, UK.
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
ORCID: 0000-0001-8117-742X

Alejandro Martinez-Carrasco (A)

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
UCL Movement Disorders Centre, University College London, London WC1N 3BG, UK.
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.

Ruth Chia (R)

Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20814, USA.
ORCID: 0000-0002-4709-7423

Michael A Lawton (MA)

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK.
ORCID: 0000-0002-3419-0354

Maryam Shoai (M)

Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Department of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.
UK Dementia Research Institute, University College London, London WC1E 6BT, UK.

Catherine Bresner (C)

Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, UK.
ORCID: 0000-0003-2673-9762

Cornelis Blauwendraat (C)

Integrative Neurogenomics Unit, National Institute on Aging, Bethesda, MD 20814, USA.
Center for Alzheimer's and Related Dementias, National Institute on Aging, Bethesda, MD 20892, USA.
ORCID: 0000-0001-9358-8111

Andrew B Singleton (AB)

Center for Alzheimer's and Related Dementias, National Institute on Aging, Bethesda, MD 20892, USA.

Mina Ryten (M)

Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Genetics and Genomic Medicine, NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London WC1N 1EH, UK.
UK Dementia Research Institute at The University of Cambridge, Cambridge, UK.
Department of Clinical Neurosciences, School of Clinical Medicine, The University of Cambridge, Cambridge, UK.
ORCID: 0000-0001-9520-6957

Sonja W Scholz (SW)

Neurodegenerative Diseases Research Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA.
ORCID: 0000-0002-6623-0429

Bryan J Traynor (BJ)

Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20814, USA.
Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD 21287, USA.
Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK.

Nigel M Williams (NM)

Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, UK.
ORCID: 0000-0003-1177-6931

Michele T M Hu (MTM)

Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, University of Oxford, Oxford OX3 9DU, UK.
Oxford Parkinson's Disease Centre, University of Oxford, Oxford OX1 3QU, UK.
ORCID: 0000-0001-6382-5841

Yoav Ben-Shlomo (Y)

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK.

Donald G Grosset (DG)

School of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK.
ORCID: 0000-0002-2757-8203

John Hardy (J)

Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Department of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.
UK Dementia Research Institute, University College London, London WC1E 6BT, UK.
Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK.
National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, London W1T 7DN, UK.
Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong SAR, China.

Huw R Morris (HR)

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
UCL Movement Disorders Centre, University College London, London WC1N 3BG, UK.
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
ORCID: 0000-0002-5473-3774

Classifications MeSH