Accelerating Medicines Partnership: Parkinson's Disease. Genetic Resource.
Accelerating Medicines Partnership: Parkinson's Disease. Genetic Resource.
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DOI：
10.1002/mds.28549
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
AMP PD consortium
中科院分区：
文献类型：
--
作者：
Iwaki H;Leonard HL;Makarious MB;Bookman M;Landin B;Vismer D;Casey B;Gibbs JR;Hernandez DG;Blauwendraat C;Vitale D;Song Y;Kumar D;Dalgard CL;Sadeghi M;Dong X;Misquitta L;Scholz SW;Scherzer CR;Nalls MA;Biswas S;Singleton AB;Uniformed Services University of the Health Sciences Associates;AMP PD Whole Genome Sequencing Working Group;AMP PD consortium
全基因组测序数据可从多种疾病和性状的几项大型研究中获得。然而，使用这些数据需要大量的存储和计算资源，并且为了获得足够的发现能力，多个队列的协调是至关重要的。加速药物伙伴关系帕金森病项目开发了一个帕金森病（PD）研究平台，该平台集成了全基因组测序数据、RNA表达数据和临床数据的存储和分析，并在多个队列研究中协调一致。第1版包含来自4个队列的3941名参与者的全基因组测序数据。通过TOPMed Freeze 9变体调用管道对样本进行联合基因分型。我们使用加速药物合作伙伴帕金森病平台对这些全基因组测序数据进行了描述性分析。第1版中参与者的临床诊断包括2005例特发性PD患者、963例健康对照、64例前驱期受试者、62例无多巴胺缺乏证据的临床诊断PD受试者和705例携带PD风险相关GBA变体或LRRK2变体的遗传富集队列参与者，其中304例受影响。我们在特发性PD组中没有观察到致病性变异的显著富集，但在非遗传富集队列和遗传富集队列中，PD的多基因风险评分较高。人口分析显示，基因丰富的群体和德系犹太人血统之间存在相关性。我们描述了加速药物伙伴关系帕金森病平台的遗传组成部分，这是一种使PD研究社区的数据访问和分析民主化的解决方案。版权所有© 2021作者。运动障碍由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。本条目属于美国政府作品，在美国属于公有领域。
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.
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影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
影响因子：
25
作者：
Sanders SJ;Neale BM;Huang H;Werling DM;An JY;Dong S;Whole Genome Sequencing for Psychiatric Disorders (WGSPD);Abecasis G;Arguello PA;Blangero J;Boehnke M;Daly MJ;Eggan K;Geschwind DH;Glahn DC;Goldstein DB;Gur RE;Handsaker RE;McCarroll SA;Ophoff RA;Palotie A;Pato CN;Sabatti C;State MW;Willsey AJ;Hyman SE;Addington AM;Lehner T;Freimer NB
通讯作者：
Freimer NB
影响因子：
30.8
作者：
Loh, Po-Ru;Danecek, Petr;Palamara, Pier Francesco;Fuchsberger, Christian;Reshef, Yakir A.;Finucane, Hilary K.;Schoenherr, Sebastian;Forer, Lukas;McCarthy, Shane;Abecasis, Goncalo R.;Durbin, Richard;Price, Alkes L.
通讯作者：
Price, Alkes L.
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
14.5
作者：
Blauwendraat, Cornelis;Reed, Xylena;Singleton, Andrew B.
通讯作者：
Singleton, Andrew B.