# Systematic analysis of functional 3’ UTR genetic variants and their relevance to Alzheimer’s Disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $551,285

## Abstract

Project Summary
The goal of this project is to identify and characterize functional 3’ UTR genetic variants that alter
post-transcriptional regulation of mRNA abundance, with a focus on variants relevant to
Alzheimer’s disease (AD). Recently, an increasing number of genetic variants have been
cataloged that confer risks to human diseases, including AD. However, it remains a great
challenge to identify causal variants and elucidate their potential function relevant to disease
pathogenesis and progression. Compared to the progress in pinpointing genetic variants that
alter transcriptional regulation or protein-coding sequences, how genetic variants may affect
post-transcriptional processes is poorly understood. Many of the newly identified AD-associated
variants reside in non-coding regions, such as introns and 3’ UTRs, that may confer regulatory
function to the related gene, especially at the level of post-transcriptional regulation. In particular,
the 3’ UTRs of human genes are enriched with many cis-regulatory elements recognized by
trans-factors, such as RNA-binding proteins (RBPs). Together, these cis-elements and
trans-factors dictate many aspects of the mRNA that affect the final expression of a gene. mRNA
abundance of a number of well-known AD-relevant genes are regulated by RBPs or microRNAs
bound to their 3’ UTRs. Genetic variants that affect these regulatory mechanisms will lead to
abnormal mRNA expression, thus significantly altering related functional pathways. In this
project, we will leverage the large collection of public data sets on RBP-RNA interaction profiling,
RNA-seq and genotyping data collected from AD and control subjects, and our in-house data
generation. We will develop and apply novel methodologies to make full use of these data sets,
complemented by further bioinformatic prediction and high-throughput experimental testing, to
pinpoint 3’ UTR genetic variants that alter mRNA abundance in AD. This work will allow a
previously unattained level of understanding of genetic variants in post-transcriptional regulation
and provide new means to tackle the imperative task of functional interpretation of genetic
variants in AD.

## Key facts

- **NIH application ID:** 10344561
- **Project number:** 1R01AG075206-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Xinshu Grace Xiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $551,285
- **Award type:** 1
- **Project period:** 2022-02-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10344561

## Citation

> US National Institutes of Health, RePORTER application 10344561, Systematic analysis of functional 3’ UTR genetic variants and their relevance to Alzheimer’s Disease (1R01AG075206-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10344561. Licensed CC0.

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