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.

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.

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.

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.

我们通过使用多基因风险评分 (PRS) 与 PD 幻觉的发生来检查阿尔茨海默病 (AD)、精神分裂症 (SZ) 和帕金森病 (PD) 的遗传结构的假设重叠。

我们使用 2 项基于人群的研究（挪威 ParkWest 和美国帕金森环境与基因）为我们提供了 399 名具有欧洲血统且 55 岁后诊断为 PD 的 PD 患者，以评估 4 种 PRS 与 5 年后幻觉之间的关联平均病程。基于现有的其他大型联盟的全基因组关联研究，创建了 4 个 PRS：一个使用 AD、SZ 和 PD 队列，另一个用于身高的 PRS，作为阴性对照。

随着 AD-PRS 的每个 SD 增加，观察到幻觉的发生率更高（优势比 [OR]：1.37，95% 置信区间 [CI]：1.03-1.83）。这种效应主要是由APOE驱动的（OR：1.92，95% CI：1.14-3.22）。此外，使用 SZ-PRS 和 PD-PRS 分别观察到幻觉患病率的暗示性降低和增加（OR：0.77，95% CI：0.59-1.01；和 OR：1.29，95% CI：0.95- 1.76，分别）。没有观察到与身高 PRS 的关联。

这些结果表明，PD 中的幻觉机制可能部分是由导致 AD 认知能力下降的相同遗传结构驱动的，尤其是由APOE驱动。