TY - JOUR
T1 - Accelerating Medicines Partnership
T2 - Parkinson's Disease. Genetic Resource
AU - Uniformed Services University of the Health Sciences Associates
AU - AMP PD Whole Genome Sequencing Working Group
AU - AMP PD consortium
AU - Iwaki, Hirotaka
AU - Leonard, Hampton L.
AU - Makarious, Mary B.
AU - Bookman, Matt
AU - Landin, Barry
AU - Vismer, David
AU - Casey, Bradford
AU - Gibbs, J. Raphael
AU - Hernandez, Dena G.
AU - Blauwendraat, Cornelis
AU - Vitale, Daniel
AU - Song, Yeajin
AU - Kumar, Dinesh
AU - Dalgard, Clifton L.
AU - Sadeghi, Mahdiar
AU - Dong, Xianjun
AU - Misquitta, Leonie
AU - Scholz, Sonja W.
AU - Scherzer, Clemens R.
AU - Nalls, Mike A.
AU - Biswas, Shameek
AU - Singleton, Andrew B.
N1 - Funding Information:
Support for this study came from Accelerating Medicines Partnership in Parkinson's Disease (AMP PD), a public‐private partnership managed by the FNIH and funded by Celgene, GSK, the Michael J. Fox Foundation for Parkinson's Research, the National Institute of Neurological Disorders and Stroke, Pfizer, Sanofi, and Verily. This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services project ZO1 AG000949 and grants from the Department of Defense (IAA‐XAG16001‐001‐00000) and the Michael J. Fox Foundation for Parkinson's Research. This research was supported in part by the Intramural Research Program of the National Institutes of Health (National Institute on Aging, National Institute of Neurological Disorders and Stroke project numbers 1ZIAAG000935 and 1ZIANS003154). Funding agencies:
Funding Information:
Andrew Singleton received grants from the Michael J. Fox Foundation for Parkinson's Research and the Department of Defense NETPR Program (grant IAA‐XAG16001‐001‐00000). Sonja W. Scholz received support from the Intramural Research Program of the National Institute of Health (National Institute on Aging, National Institute of Neurological Disorders and Stroke; project numbers 1ZIAAG000935, 1ZIANS003154). Relevant conflicts of interest/financial disclosures:
Funding Information:
AMP PD, a public-private partnership, is managed by the FNIH and funded by Celgene, GSK, the Michael J. Fox Foundation for Parkinson's Research, the National Institute of Neurological Disorders and Stroke, Pfizer, Sanofi, and Verily. Data used in the preparation of this article were obtained from the AMP PD Knowledge Platform. For up-to-date information on the study, go to https://www.amp-pd.org. Clinical data and biosamples used in preparation of this article were obtained from the Fox Investigation for New Discovery of Biomarkers (BioFIND), the Harvard Biomarker Study (HBS), the Parkinson's Progression Markers Initiative (PPMI), and the Parkinson's Disease Biomarkers Program (PDBP). BioFIND is sponsored by the Michael J. Fox Foundation for Parkinson's Research (MJFF) with support from the National Institute for Neurological Disorders and Stroke (NINDS). The BioFIND Investigators have not participated in reviewing the data analysis or content of the article. For up-to-date information on the study, visit michaeljfox.org/biofind. The Harvard Biomarkers Study (HBS) is a collaboration of HBS investigators (full list of HBS investigator found at https://www.bwhparkinsoncenter.org/biobank/) and funded through philanthropy and NIH and Non-NIH funding sources. The HBS Investigators have not participated in reviewing the data analysis or content of the article. PPMI, a public-private partnership, is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners (the full names of all the PPMI funding partners can be found at www.ppmi-info.org/fundingpartners. The PPMI Investigators have not participated in reviewing the data analysis or content of the article. For up-to-date information on the study, visit www.ppmi-info.org. The Parkinson's Disease Biomarker Program (PDBP) consortium is supported by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health. A full list of PDBP investigators can be found at https://pdbp.ninds.nih.gov/policy. The PDBP Investigators have not participated in reviewing the data analysis or content of the article. Participation by individuals employed by Data Tecnica International LLC was supported in part by a consulting contract between the National Institutes of Health (NIA/NINDS) and the company. Individuals employed by Data Tecnica International LLC report no conflict of interest relating to the work carried out in this report.
Funding Information:
AMP PD, a public‐private partnership, is managed by the FNIH and funded by Celgene, GSK, the Michael J. Fox Foundation for Parkinson's Research, the National Institute of Neurological Disorders and Stroke, Pfizer, Sanofi, and Verily. Data used in the preparation of this article were obtained from the AMP PD Knowledge Platform. For up‐to‐date information on the study, go to https://www.amp-pd.org . Clinical data and biosamples used in preparation of this article were obtained from the Fox Investigation for New Discovery of Biomarkers (BioFIND), the Harvard Biomarker Study (HBS), the Parkinson's Progression Markers Initiative (PPMI), and the Parkinson's Disease Biomarkers Program (PDBP). BioFIND is sponsored by the Michael J. Fox Foundation for Parkinson's Research (MJFF) with support from the National Institute for Neurological Disorders and Stroke (NINDS). The BioFIND Investigators have not participated in reviewing the data analysis or content of the article. For up‐to‐date information on the study, visit michaeljfox.org/biofind . The Harvard Biomarkers Study (HBS) is a collaboration of HBS investigators (full list of HBS investigator found at https://www.bwhparkinsoncenter.org/biobank/ ) and funded through philanthropy and NIH and Non‐NIH funding sources. The HBS Investigators have not participated in reviewing the data analysis or content of the article. PPMI, a public‐private partnership, is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners (the full names of all the PPMI funding partners can be found at www.ppmi-info.org/fundingpartners . The PPMI Investigators have not participated in reviewing the data analysis or content of the article. For up‐to‐date information on the study, visit www.ppmi-info.org . The Parkinson's Disease Biomarker Program (PDBP) consortium is supported by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health. A full list of PDBP investigators can be found at https://pdbp.ninds.nih.gov/policy . The PDBP Investigators have not participated in reviewing the data analysis or content of the article. Participation by individuals employed by Data Tecnica International LLC was supported in part by a consulting contract between the National Institutes of Health (NIA/NINDS) and the company. Individuals employed by Data Tecnica International LLC report no conflict of interest relating to the work carried out in this report.
Publisher 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.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - Parkinson's disease
KW - clinical
KW - genetics
KW - open science
UR - http://www.scopus.com/inward/record.url?scp=85105204283&partnerID=8YFLogxK
U2 - 10.1002/mds.28549
DO - 10.1002/mds.28549
M3 - Article
C2 - 33960523
AN - SCOPUS:85105204283
SN - 0885-3185
VL - 36
SP - 1795
EP - 1804
JO - Movement Disorders
JF - Movement Disorders
IS - 8
ER -