Genetic investigation in neurodegenerative conditions
- PI
- Coppola, Giovanni
- DAR ID
- 10196
- Initial Approval Date
- February 2, 2024
- Current DAR Status
- Active
- PI Institution
- Regeneron Pharmaceuticals
- PI Institution Country
- United States
- PI Institution Type
- For-Profit
Requested Datasets (1)
Research Use Statement
Objective: To leverage large-scale electronic health care record data and biomarkers of neurodegeneration to improve gene discovery in Alzheimer’s disease.
Study design: The goal of our work is to integrate common and rare genetic variation across multiple cohorts with the genetic data collected in the ADSP to improve gene discovery in Alzheimer’s disease (AD) and related neurodegenerative conditions. We plan to perform both genome-wide and exome-wide association analyses (GWAS/ExWAS) with phenotypes including any dementia, AD, mild cognitive impairment (MCI), age of onset for cognitive decline, and quantitative readouts of neurodegeneration including cognitive tests and brain MRI measures where available. We will integrate our findings with expression quantitative trait loci and single cell gene expression to understand pathways and mechanisms modulating risk for these phenotypes.
Analysis plan: First, we will integrate data from ADSP with electronic health and genetic data at the Regeneron Genetics Center (RGC) to harmonize both genetic variation and phenotype data. Next, we will use standard approaches to perform GWAS/ExWAS, perform meta-analysis across cohorts, and post-GWAS analyses to annotate our findings across traits. All data will remain anonymized and securely stored, we will not share any of the individual level data outside of Regeneron or beyond the researchers on our application. We have a secure computational environment to store these data and IT staff dedicated to ensuring we comply with the necessary requirements delineated by the NIAGADS.
Study design: The goal of our work is to integrate common and rare genetic variation across multiple cohorts with the genetic data collected in the ADSP to improve gene discovery in Alzheimer’s disease (AD) and related neurodegenerative conditions. We plan to perform both genome-wide and exome-wide association analyses (GWAS/ExWAS) with phenotypes including any dementia, AD, mild cognitive impairment (MCI), age of onset for cognitive decline, and quantitative readouts of neurodegeneration including cognitive tests and brain MRI measures where available. We will integrate our findings with expression quantitative trait loci and single cell gene expression to understand pathways and mechanisms modulating risk for these phenotypes.
Analysis plan: First, we will integrate data from ADSP with electronic health and genetic data at the Regeneron Genetics Center (RGC) to harmonize both genetic variation and phenotype data. Next, we will use standard approaches to perform GWAS/ExWAS, perform meta-analysis across cohorts, and post-GWAS analyses to annotate our findings across traits. All data will remain anonymized and securely stored, we will not share any of the individual level data outside of Regeneron or beyond the researchers on our application. We have a secure computational environment to store these data and IT staff dedicated to ensuring we comply with the necessary requirements delineated by the NIAGADS.
Non-Technical Summary
Therapeutic development in Alzheimer’s disease has greatly benefitted from understanding the genetics of this disorder. However, the role of rare genetic variation and the impact of genetics on biomarkers in Alzheimer’s remain mostly unknown. Our goal is to develop new therapies, and the data from the ADSP will help us prioritize potential molecules and pathways to pursue in Alzheimer’s disease and related conditions.
Reported Publications
Publications shown are those reported by investigators through NIAGADS DAR reporting and renewal processes and may not represent a complete list of publications associated with the project.
No publications have been reported for this DAR.