Accelerating Medicines Partnership: Parkinson's Disease. Genetic Resource.
Parkinson's disease
clinical
genetics
open science
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
20
01
2021
received:
04
12
2020
accepted:
11
02
2021
pubmed:
8
5
2021
medline:
1
9
2021
entrez:
7
5
2021
Statut:
ppublish
Résumé
Whole-genome sequencing data are available from several large studies across a variety of diseases and traits. However, massive storage and computation resources are required to use these data, and to achieve sufficient power for discoveries, harmonization of multiple cohorts is critical. The Accelerating Medicines Partnership Parkinson's Disease program has developed a research platform for Parkinson's disease (PD) that integrates the storage and analysis of whole-genome sequencing data, RNA expression data, and clinical data, harmonized across multiple cohort studies. The version 1 release contains whole-genome sequencing data derived from 3941 participants from 4 cohorts. Samples underwent joint genotyping by the TOPMed Freeze 9 Variant Calling Pipeline. We performed descriptive analyses of these whole-genome sequencing data using the Accelerating Medicines Partnership Parkinson's Disease platform. The clinical diagnosis of participants in version 1 release includes 2005 idiopathic PD patients, 963 healthy controls, 64 prodromal subjects, 62 clinically diagnosed PD subjects without evidence of dopamine deficit, and 705 participants of genetically enriched cohorts carrying PD risk-associated GBA variants or LRRK2 variants, of whom 304 were affected. We did not observe significant enrichment of pathogenic variants in the idiopathic PD group, but the polygenic risk score was higher in PD both in nongenetically enriched cohorts and genetically enriched cohorts. The population analysis showed a correlation between genetically enriched cohorts and Ashkenazi Jewish ancestry. We describe the genetic component of the Accelerating Medicines Partnership Parkinson's Disease platform, a solution to democratize data access and analysis for the PD research community. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article is a U.S. Government work and is in the public domain in the USA.
Sections du résumé
BACKGROUND
Whole-genome sequencing data are available from several large studies across a variety of diseases and traits. However, massive storage and computation resources are required to use these data, and to achieve sufficient power for discoveries, harmonization of multiple cohorts is critical.
OBJECTIVES
The Accelerating Medicines Partnership Parkinson's Disease program has developed a research platform for Parkinson's disease (PD) that integrates the storage and analysis of whole-genome sequencing data, RNA expression data, and clinical data, harmonized across multiple cohort studies.
METHODS
The version 1 release contains whole-genome sequencing data derived from 3941 participants from 4 cohorts. Samples underwent joint genotyping by the TOPMed Freeze 9 Variant Calling Pipeline. We performed descriptive analyses of these whole-genome sequencing data using the Accelerating Medicines Partnership Parkinson's Disease platform.
RESULTS
The clinical diagnosis of participants in version 1 release includes 2005 idiopathic PD patients, 963 healthy controls, 64 prodromal subjects, 62 clinically diagnosed PD subjects without evidence of dopamine deficit, and 705 participants of genetically enriched cohorts carrying PD risk-associated GBA variants or LRRK2 variants, of whom 304 were affected. We did not observe significant enrichment of pathogenic variants in the idiopathic PD group, but the polygenic risk score was higher in PD both in nongenetically enriched cohorts and genetically enriched cohorts. The population analysis showed a correlation between genetically enriched cohorts and Ashkenazi Jewish ancestry.
CONCLUSIONS
We describe the genetic component of the Accelerating Medicines Partnership Parkinson's Disease platform, a solution to democratize data access and analysis for the PD research community. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article is a U.S. Government work and is in the public domain in the USA.
Identifiants
pubmed: 33960523
doi: 10.1002/mds.28549
pmc: PMC8453903
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1795-1804Subventions
Organisme : NINDS NIH HHS
ID : R01 NS115144
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS120637
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA NS003154
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AG000935
Pays : United States
Informations de copyright
© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article is a U.S. Government work and is in the public domain in the USA.
Références
PLoS Genet. 2019 Dec 12;15(12):e1008489
pubmed: 31830040
J Med Genet. 2020 May;57(5):331-338
pubmed: 31784483
Mov Disord. 2019 Jun;34(6):866-875
pubmed: 30957308
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Cell. 2019 Mar 21;177(1):70-84
pubmed: 30901550
Mov Disord. 2016 Jan;31(1):79-85
pubmed: 26268663
Nat Commun. 2018 Oct 2;9(1):4038
pubmed: 30279509
Neurobiol Aging. 2015 Mar;36(3):1605.e7-12
pubmed: 25444595
Fly (Austin). 2012 Apr-Jun;6(2):80-92
pubmed: 22728672
Mov Disord. 2020 May;35(5):774-780
pubmed: 31958187
Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067
pubmed: 29165669
Eur J Hum Genet. 2012 Jun;20(6):598-606
pubmed: 22333897
Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16222-7
pubmed: 20798349
Brain. 2019 Jan 1;143(1):234-248
pubmed: 31755958
Nature. 2010 Sep 2;467(7311):52-8
pubmed: 20811451
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Lancet Neurol. 2019 Dec;18(12):1091-1102
pubmed: 31701892
Mov Disord. 2019 Dec;34(12):1839-1850
pubmed: 31505070
Nat Neurosci. 2017 Dec;20(12):1661-1668
pubmed: 29184211
Nat Genet. 2016 Nov;48(11):1443-1448
pubmed: 27694958
Nat Rev Drug Discov. 2019 Feb 27;:
pubmed: 30936505
Nat Genet. 2018 May;50(5):727-736
pubmed: 29700473