Pleiotropy GWAS of Alzheimer's Diseases

Grants and Contracts Details


“Pleiotropy GWAS of Alzheimer’s Disease and Multiple Neurodegenerative Diseases” This proposal describes plans to co-analyze genome-wide association study GWAS datasets of late-onset Alzheimer’s disease (LOAD) with GWAS datasets of other neurodegenerative diseases (NDs) including Parkinson’s disease, Frontotemporal Dementria, Progressive Supranuclear Palsy, and Multiple Sclerosis. Although across NDs there are many distinct pathological features, some shared features, such protein aggregation in the brain are common to multiple NDs, suggesting that genetic studies combining NDs may identify pleiotropic genetic risk factors which may not have been identified in studies of individual NDs. The goal of these planned analyses is to identify genes with effects across LOAD and other NDs (pleiotropy). Our approach will include more broad hypothesis-free analyses such as an across-ND “mega-analysis” (GWAS meta-analysis), as well as more targeted “drill down” approaches like using targeted pathway analyses (e.g., tau hyperphosphorylation, inflammation pathways) to examine known biological pathways and to identify novel biological pathways shared across NDs. These analyses use publicly available data and advance the mandate set forward in the National Institute on Aging (NIA) RFA PA-13-168 (“Secondary Analyses of Existing Data Sets and Stored Biospecimens to Address Clinical Aging Research Questions”) specifically by examining (1) “Interactions among disease processes and health outcomes in complex older patients”, (2) “Analysis and meta-analysis of existing data sets to inform designs of future clinical trials” (in that by examining biological pathways as part of analysis, we will be trying to identify ‘druggable targets’), and (3) more loosely the “effects of specific combinations of two or more comorbid conditions or combinations of medications on adverse health outcomes”, as the prospective aging studies analyzed include individuals with AD comorbid with other neurodegenerative diseases or features. By combining genetic analyses of AD with other NDs, we will identify pleiotropic genetic risk factors which will provide targets for pharmaceutical development not only in AD, but possibly for NDs with similar pathologic features as well
Effective start/end date9/15/164/30/22


  • University of Pennsylvania: $461,246.00


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