Abstract
Objective We examine the hypothesized overlap of genetic architecture for Alzheimer disease (AD), schizophrenia (SZ), and Parkinson disease (PD) through the use of polygenic risk scores (PRSs) with the occurrence of hallucinations in PD.
Methods We used 2 population-based studies (ParkWest, Norway, and Parkinson's Environment and Gene, USA) providing us with 399 patients with PD with European ancestry and a PD diagnosis after age 55 years to assess the associations between 4 PRSs and hallucinations after 5 years of mean disease duration. Based on the existing genome-wide association study of other large consortia, 4 PRSs were created: one each using AD, SZ, and PD cohorts and another PRS for height, which served as a negative control.
Results A higher prevalence of hallucinations was observed with each SD increase of the AD-PRS (odds ratio [OR]: 1.37, 95% confidence interval [CI]: 1.03–1.83). This effect was mainly driven by APOE (OR: 1.92, 95% CI: 1.14–3.22). In addition, a suggestive decrease and increase, respectively, in hallucination prevalence were observed with the SZ-PRS and the PD-PRS (OR: 0.77, 95% CI: 0.59–1.01; and OR: 1.29, 95% CI: 0.95–1.76, respectively). No association was observed with the height PRS.
Conclusions These results suggest that mechanisms for hallucinations in PD may in part be driven by the same genetic architecture that leads to cognitive decline in AD, especially by APOE.
Glossary
- AD=
- Alzheimer disease;
- aOR=
- adjusted odds ratio;
- CI=
- confidence interval;
- GWAS=
- genome-wide association study;
- MDS-UPDRS=
- Movement Disorder Society–Unified Parkinson Disease Rating Scale;
- MMSE=
- Mini-Mental State Examination;
- PD=
- Parkinson disease;
- PEG=
- Parkinson's Environment and Gene;
- PK=
- ParkWest;
- PRS=
- polygenic risk score;
- SZ=
- schizophrenia
Footnotes
Go to Neurology.org/NG for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by F32AG063442.
- Received April 6, 2020.
- Accepted in final form May 26, 2020.
- Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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