| Autor: |
Andrew B. Singleton, Xianjun Dong, David Vismer, Matt Bookman, Leonie Misquitta, Cornelis Blauwendraat, Mahdiar Sadeghi, Yeajin Song, Sonja W. Scholz, Barry Landin, Hirotaka Iwaki, J. Raphael Gibbs, Clifton L. Dalgard, Mary B. Makarious, Mike A. Nalls, Hampton L. Leonard, Dinesh Kumar, Shameek Biswas, Daniel Vitale, Clemens R. Scherzer, Bradford Casey, Dena G. Hernandez |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
BackgroundWhole-genome sequencing (WGS) data is 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 the sufficient power for discoveries, harmonization of multiple cohorts is critical.ObjectivesThe Accelerating Medicines Partnership Parkinson’s Disease (AMP PD) program has developed a research platform for Parkinson’s disease (PD) which integrates the storage and analysis of WGS data, RNA expression data, and clinical data, harmonized across multiple cohort studies.MethodsThe version 1 release contains WGS data derived from 3,941 participants from 4 cohorts. Samples underwent joint genotyping by the TOPMed Freeze 9 Variant Calling Pipeline. We performed descriptive analyses of these WGS data using the AMP PD platform.ResultsThe clinical diagnosis of participants in version 1 release includes 2,005 idiopathic PD patients, 963 healthy controls, 64 prodromal subjects, 62 clinically diagnosed PD subjects without evidence of dopamine deficit (SWEDD) and 705 participants of genetically enriched cohorts carrying PD risk associated GBA variants or LRRK2 variants in which 304 were affected. We did not observe a significant enrichment of pathogenic variants in the idiopathic PD group, but the polygenic risk score (PRS) was higher in PD both in non-genetically enriched cohorts and genetically enriched cohorts. The population analysis showed a correlation between genetically enriched cohorts and Ashkenazi Jewish ancestry.ConclusionsWe describe the genetic component of the AMP PD platform, a solution to democratise data access and analysis for the PD research community.(d) Financial Disclosure/CoI |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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