Wu Qi, Liu Shulin, Huang Xiurong, Liu Jiabin, Wang Yige, Xiang Yaqing, Tang Xuxiong, Xu Qian, Yan Xinxiang, Tang Beisha, Guo Jifeng
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China.
Front Aging Neurosci. 2023 Mar 14;15:1120615. doi: 10.3389/fnagi.2023.1120615. eCollection 2023.
Although the relationship between psychiatric disorders and Parkinson's disease (PD) has attracted continuous research attention, the causal linkage between them has not reached a definite conclusion.
To identify the causal relationship between psychiatric disorders and PD, we used public summary-level data from the most recent and largest genome-wide association studies (GWASs) on psychiatric disorders and PD to conduct a bidirectional two-sample Mendelian randomization (MR). We applied stringent control steps in instrumental variable selection using the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method to rule out pleiotropy. The inverse-variance weighted (IVW) method was used to identify the causal relationship between psychiatric disorders and PD. Multiple MR analysis methods, including MR-Egger, weighted-median, and leave-one-out analyses, were used for sensitivity analysis, followed by heterogeneity tests. Further validation and reverse MR analyses were conducted to strengthen the results of the forward MR analysis.
The lack of sufficient estimation results could suggest a causal relationship between psychiatric disorders and PD in the forward MR analysis. However, the subsequent reverse MR analysis detected a causal relationship between PD and bipolar disorder (IVW: odds ratios [OR] =1.053, 95% confidence interval [CI] =1.02-1.09, = 0.001). Further analysis demonstrated a causal relationship between genetically predicted PD and the risk of bipolar disorder subtype. No pleiotropy or heterogeneity was detected in the analyses.
Our study suggested that while psychiatric disorders and traits might play various roles in the risk of developing PD, PD might also be involved in the risk of developing psychiatric disorders.
尽管精神障碍与帕金森病（PD）之间的关系一直是研究的热点，但两者之间的因果联系尚未有定论。
为了确定精神障碍与PD之间的因果关系，我们使用了来自最新和最大规模的精神障碍与PD全基因组关联研究（GWAS）的公开汇总数据，进行双向双样本孟德尔随机化（MR）分析。我们采用孟德尔随机化多效性残差和离群值（MR-PRESSO）方法，在工具变量选择中应用严格的控制步骤以排除多效性。采用逆方差加权（IVW）方法来确定精神障碍与PD之间的因果关系。使用包括MR-Egger、加权中位数和留一法分析在内的多种MR分析方法进行敏感性分析，随后进行异质性检验。进一步进行验证和反向MR分析以强化正向MR分析的结果。
正向MR分析中缺乏足够的估计结果可能提示精神障碍与PD之间存在因果关系。然而，随后的反向MR分析检测到PD与双相情感障碍之间存在因果关系（IVW：比值比[OR]=1.053，95%置信区间[CI]=1.02 - 1.09，P = 0.001）。进一步分析表明，遗传预测的PD与双相情感障碍亚型风险之间存在因果关系。分析中未检测到多效性或异质性。
我们的研究表明，虽然精神障碍及其特征可能在PD发病风险中发挥多种作用，但PD也可能参与精神障碍的发病风险。
