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Principal Investigator  
Principal Investigator's Name: Brian Fulton-Howard
Institution: Icahn School of Medicine at Mount Sinai
Department: Genetics
Country:
Proposed Analysis: We propose to generate a Polygenic Risk Score (PRS) model and find rare variants that are associated with deviation from PRS disease state predictions, as well as novel Alzheimer's Disease (AD) risk related phenotypes. (Escott-Price et al. 2015) have shown PRSs to be predictive of AD status, and deviation of PRS from actual disease outcome, Δ, has identified subjects enriched with rare risk alleles for Crohn's Disease (Jostins, Levine, and Barrett 2013). We will make predictions of disease status in the Alzheimer's Disease Sequencing Project (ADSP), based on PRS-based models generated from a non-ADSP ADGC sample, including the Adult Changes in Thought study. We will then identify rare genetic variants that are associated with departure from those predictions. We also intend to use the PRS model generated for this study to investigate the overlap between AD risk and liability for other, putatively unrelated traits in order to identify phenotypes with shared risk architecture. Our hypothesis is that we will be able to increase power for the discovery of rare variants by using Δs from our model predictions as a response variable. We also expect at least some rare variation to be associated with departure from common risk. For this Polygenic Phenome Wide Association Study (PolyPheWAS), we have access to a genotyped and deeply phenotyped sample through an institutional biobank. Overall, a PRS model generated from ADGC data will allow us to identify rare variants and non AD traits associated with AD risk.
Additional Investigators  
Investigator's Name: Tulsi Patel
Proposed Analysis: Will focus on extremes association study but may be involved with all analyses.
Investigator's Name: Alison Goate
Proposed Analysis: Alison Goate will be supervising all analyses as PI of the group.
Investigator's Name: Nadia Harerimana
Proposed Analysis: Investigator will perform analyses for all aims, using ADNI data, ADSP data and ADGC data. Analyses will include but not be limited to PRS and Association analyses.
Investigator's Name: Jessica Schulman
Proposed Analysis: Investigator will perform analyses for all aims, using ADNI data, ADSP data and ADGC data. Analyses will include but not be limited to PRS and Association analyses.
Investigator's Name: Yiyuan Liu
Proposed Analysis: Investigator will perform analyses for all aims, using ADNI data, ADSP data and ADGC data. Analyses will include but not be limited to PRS and Association analyses.
Investigator's Name: Travyse Edwards
Proposed Analysis: Investigator will perform analyses for all aims, using ADNI data, ADSP data and ADGC data. Analyses will include but not be limited to PRS and Association analyses.
Investigator's Name: Bianca Esposito Aristel
Proposed Analysis: Investigator will perform analyses for all aims, using ADNI data, ADSP data and ADGC data. Analyses will include but not be limited to PRS and Association analyses.
Investigator's Name: Wen Huang
Proposed Analysis: Investigator will be involved in data processing and storage
Investigator's Name: Hei Man Wu
Proposed Analysis: Investigator may perform analyses for all aims, using ADNI data, ADSP data and ADGC data. Analyses will include but not be limited to PRS. Investigator will also be involved in data processing and storage.
Investigator's Name: Lili Gai
Proposed Analysis: Investigator will be involved in data processing and storage as the Director for Computational and Data Ecosystem
Investigator's Name: Paul O'Reilly
Proposed Analysis: Investigator will perform analyses for all aims, using ADNI data, ADSP data and ADGC data. Analyses will include but not be limited to PRS and Association analyses. Investigator may be involved in data processing and storage
Investigator's Name: Edoardo Marcora
Proposed Analysis: Investigator will be supervising analyses, working on association studies and performing other analyses enumerated in the main project
Investigator's Name: Alan Renton
Proposed Analysis: Investigator will focus on association studies but will be involved with all approved analyses