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. 2021 Aug;36(8):1795-1804.
doi: 10.1002/mds.28549. Epub 2021 May 7.

Accelerating Medicines Partnership: Parkinson's Disease. Genetic Resource

Hirotaka Iwaki  1   2   3 , Hampton L Leonard  1   2   3 , Mary B Makarious  3 , Matt Bookman  4 , Barry Landin  5 , David Vismer  5 , Bradford Casey  6 , J Raphael Gibbs  3 , Dena G Hernandez  3 , Cornelis Blauwendraat  3 , Daniel Vitale  1   2   3 , Yeajin Song  1   2   3 , Dinesh Kumar  7 , Clifton L Dalgard  8   9 , Mahdiar Sadeghi  7   10 , Xianjun Dong  11 , Leonie Misquitta  12 , Sonja W Scholz  13   14 , Clemens R Scherzer  11 , Mike A Nalls  1   2   3 , Shameek Biswas  15 , Andrew B Singleton  2   3 ; Uniformed Services University of the Health Sciences Associates; AMP PD Whole Genome Sequencing Working Group; AMP PD consortium
Affiliations

Accelerating Medicines Partnership: Parkinson's Disease. Genetic Resource

Hirotaka Iwaki et al. Mov Disord. 2021 Aug.

Abstract

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.

Keywords: Parkinson's disease; clinical; genetics; open science.

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Figures

FIG 1
FIG 1
WGS sample flowchart. WGS, whole‐genome sequencing; QC, quality control. [Color figure can be viewed at wileyonlinelibrary.com]
FIG 2
FIG 2
Density plots for polygenic risk score. HC, healthy volunteers; PD, participants with Parkinson's disease; SWEDD, scan without evidence of dopamine deficit. PRS90 is a weighted sum of the independent risk loci reported in Nalls et al (2019). PRS83 is the same but removing the 7 variants in GBA, LRRK2, and SNCA regions. [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

References

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