# Single nucleotide and copy number variants associated with Parkinson disease

> **NIH VA I01** · MINNEAPOLIS VA  MEDICAL CENTER · 2020 · —

## Abstract

The Million Veteran Program (MVP) data set will be used to identify new genetic risk variants—
including copy number variants (CNVs: deletions and duplications in the genome)—for
Parkinson disease (PD). Previously identified genetic risk factors will be better characterized by
testing all pairwise gene-by-gene interactions and testing if variants associated with mRNA
expression levels are predictive of PD risk using PrediXcan. The MVP intake questionnaire
captured previously identified environmental risk factors such as head trauma (traumatic brain
injury) and pesticide exposure; these will be accounted for in the study through gene-by-
environment tests to determine if the effects of variants are mediated by these exposures. This
will also be the first GWAS of PD to analyse significant Hispanic and African American
populations, which will reveal if the variants identified using individuals of European descent are
generalizable to other populations. In addition, replication of an association between lower
mitochondrial DNA copy number (mtDNA CN) in the blood and PD will be attempted, possibly
establishing mtDNA CN as a biomarker for PD risk and progression, which could later be used
in clinical trials or even in the clinic. mtDNA CN will be measured using a novel approach that
we developed to determine the relative signal intensity for mitochondrial probes on a GWAS
array compared to the corresponding signal intensity for nuclear probes. Mendelian
randomization experiments would then be employed to see if there is evidence that low mtDNA
CN causes PD or whether the PD pathology causes the mtDNA CN to decrease. These
experiments will reveal new information regarding the biology of Parkinson disease, allow for
better risk stratification, and potentially reveal targets for novel therapeutics.

## Key facts

- **NIH application ID:** 9870784
- **Project number:** 5I01BX004184-02
- **Recipient organization:** MINNEAPOLIS VA  MEDICAL CENTER
- **Principal Investigator:** JAMES ASHE
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870784

## Citation

> US National Institutes of Health, RePORTER application 9870784, Single nucleotide and copy number variants associated with Parkinson disease (5I01BX004184-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9870784. Licensed CC0.

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