# Pleiotropy GWAS of Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $411,294

## Abstract

PROJECT SUMMARY
This proposal, entitled “Pleiotropy GWAS of Alzheimer's Disease and Multiple Neurodegenerative Diseases,”
describes plans to analyze existing neurodegenerative phenotype and genome-wide genotype data from
existing genome-wide association studies (GWAS) of multiple neurodegenerative diseases, including
Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal dementia (FTD), among others. While
neurodegenerative diseases have distinct pathologies, there are also shared pathological features like protein
aggregation in the brain (e.g., tau protein). This suggests that genetic studies combining neurodegenerative
disease genetics studies may identify genetic risk factors contributing to one or more individual NDs
(“pleiotropy”) through these common features. The goal of these planned analyses is to identify genetic loci
and variants with effects across multiple NDs. Our approach includes broad hypothesis-free analyses like
GWAS meta-analysis, as well as targeted “drill-down” approaches like pathway analyses examining known
biological pathways. These analyses will use publicly available data on genome-wide association study and
whole genome/exome sequence datasets curated by individual groups, disease-specific consortia, and on the
NIH Database of Genotypes and Phenotypes (dbGaP). This project will require extensive collection of
genotypes from well-characterized cases and controls; systematic archiving of case-control and prospective
cohort studies; a formally-structured data harmonization process; inclusion of multiethnic GWAS and
WGS/WES studies; and longitudinal analyses in cohort studies of neurodegeneration in order to fulfill the
mandate of the National Institute on Aging (NIA) RFA PAR-15-356. Our three aims include (1) harmonization
and integration of genotype and phenotype data from multiple large-scale genetic studies of differeing
neurodegenerative diseases; (2) estimating shared heritability between neurodegenerative diseases and
performing GWAS and WGS/WES association study meta-analyses; and (3) performing analyses of
intermediate and related phenotypes and incorporating functional annotation to identify truly functional
pleiotropic variants and their causal effects on multiple neurodegenerative diseases. These analyses will
examine both common and rare genomic variants and will use a similar strategy to existing genetic studies
comparing neuropsychiatric disorders (e.g, schizophrenia, depression), with refinement and development of
novel pleiotropy methods. We will leverage our considerable experience with large-scale genetic association
and meta-analysis studies to identify new genetic risk factors for neurodegenerative diseases using data on
tens of thousands of affected and unaffected individuals. Furthermore, we will create an online resource for
data harmonization and sharing analysis results with investigators interested in shared genetic risk factors of
neurodegeneration.

## Key facts

- **NIH application ID:** 9925751
- **Project number:** 5R01AG054060-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Adam Christian Naj
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $411,294
- **Award type:** 5
- **Project period:** 2016-09-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925751

## Citation

> US National Institutes of Health, RePORTER application 9925751, Pleiotropy GWAS of Alzheimer's Disease (5R01AG054060-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9925751. Licensed CC0.

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