Genetic risk scores and hallucinations in patients with Parkinson disease

Cynthia D J Kusters; Kimberly C Paul; Aline Duarte Folle; Adrienne M Keener; Jeff M Bronstein; Valerija Dobricic; Ole-Bjørn Tysnes; Lars Bertram; Guido Alves; Janet S Sinsheimer; Christina M Lill; Jodi Maple-Grødem; Beate R Ritz

doi:10.1212/NXG.0000000000000492

Genetic risk scores and hallucinations in patients with Parkinson disease

Neurol Genet. 2020 Jul 20;6(5):e492. doi: 10.1212/NXG.0000000000000492. eCollection 2020 Oct.

Affiliation

¹ Department of Epidemiology (C.D.J.K., K.C.P., A.D.F., B.R.R.), UCLA Fielding School of Public Health, Los Angeles, CA, USA; Department of Human Genetics (C.D.J.K., J.S.S.), David Geffen School of Medicine, Los Angeles, CA; Department of Neurology (A.M.K., J.M.B., B.R.R.), David Geffen School of Medicine, Los Angeles, CA; Parkinson's Disease Research (A.M.K.), Education, and Clinical Center, Greater Los Angeles Veterans Affairs Medical Center, Los Angeles, CA; Brain Research Institute (J.M.B.), University of California, Los Angeles, CA; Lübeck Interdisciplinary Platform for Genome Analytics (V.D., L.B.), Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany; Department of Neurology (O.-B.T.), Haukeland University Hospital, Bergen, Norway and University of Bergen, Bergen, Norway; Department of Clinical Medicine (O.-B.T.), University of Bergen, Bergen, Norway; Department of Psychology (L.B.), Centre for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway; The Norwegian Center for Movement Disorders (G.A., J.M.-G.), Stavanger University Hospital, Stavanger, Norway; Department of Neurology (G.A.), Stavanger University Hospital, Stavanger, Norway; Department of Chemistry (G.A., J.M.-G.), Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway; Department of Biostatistics (J.S.S.), UCLA Fielding School of Public Health, Los Angeles, CA; Department of Computational Medicine (J.S.S.), David Geffen School of Medicine, Los Angeles, CA; Section for Translational Surgical Oncology and Biobanking (C.M.L.), Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck; Ageing Epidemiology Research Unit (C.M.L.), School of Public Health, Imperial College, London, United Kingdom; and Department of Environmental Health (B.R.R.), UCLA Fielding School of Public Health, Los Angeles, CA.

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.

Genetic risk scores and hallucinations in patients with Parkinson disease

Authors

Affiliation

Abstract

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