# High resolution mapping of the genetic risk for disease in the aging brain

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $619,917

## Abstract

ABSTRACT
Brain structure undergoes changes throughout life as part of the normal healthy aging process, yet some
genetic factors embedded in our DNA are believed to alter and potentially accelerate the aging process within
the brain. While numerous neuroimaging studies have aimed to map the genetics of dementia, differences in
populations and approaches confounded with the small effect sizes attributable to any single genetic variant
leads to inconsistencies in findings and limited resources to investigate the truth. Dozens of neuroimaging
genetic studies have been collected around the world to help better understand the link. However, the
independent nature by which the studies often operate may be limiting scientific advance. Instead of collecting
new data to answer the same questions, we harmonize brain mapping efforts across existing studies and pool
information to not only study differences between the healthy and demented brain, but also examine normal
healthy aging trends, and determine the first signs of deviation, and map out the neurobiological effect of
genes that confer risk for dementia. In our effort, we aim to pinpoint mechanistic trajectories and brain circuits
by which the widely studied ApoE4 genetic haplotype affects brain throughout life. Despite being identified as a
genetic risk for Alzheimer's disease over 20 years ago, the effects on the brain in populations around the world
are remarkably inconsistent. With novel brain mapping techniques across tens of thousands of individuals
across the lifespan, we will perform the most well powered brain mapping initiative and build necessary tools to
invite other researchers from around the world to add confidence to the findings. We will also determine – with
unprecedented power -- how the aggregate risk for AD promotes accelerated brain degeneration with novel
expedited longitudinal linear mixed modeling techniques for large scale epidemiological genetic studies with
repeat data. Our proposal brings together contributions from multidisciplinary collaborators with world
renowned expertise in neurodegeneration, brain mapping, big data, artificial intelligence, epidemiology,
genomics and epigenomes, statistical genetics, and molecular and biological psychiatry. Our technical
expertise will provide resources for visualizing genetic results at the finest resolution and provide tools for
researchers to use our harmonized analyses to structure their own aging hypotheses in populations of men
and women around the world, and even target sex-specific hypotheses in aging. As new brain imaging and
genetic data is becoming rapidly available, we provide the tools to harmonize the data into this workflow for
years to come. Driven by the data sharing and reuse of this proposal, we provide a portal for researchers of
today and tomorrow to access findings from all the studies incorporated in this proposal and add to the
collective repository of effects. We hope our careful harmonization of data, alon...

## Key facts

- **NIH application ID:** 9923542
- **Project number:** 5R01AG059874-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Neda Jahanshad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $619,917
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923542

## Citation

> US National Institutes of Health, RePORTER application 9923542, High resolution mapping of the genetic risk for disease in the aging brain (5R01AG059874-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9923542. Licensed CC0.

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