Bidirectional Mendelian randomization study of psychiatric disorders and Parkinson's disease

Qi Wu; Shulin Liu; Xiurong Huang; Jiabin Liu; Yige Wang; Yaqing Xiang; Xuxiong Tang; Qian Xu; Xinxiang Yan; Beisha Tang; Jifeng Guo

doi:10.3389/fnagi.2023.1120615

Bidirectional Mendelian randomization study of psychiatric disorders and Parkinson's disease

Front Aging Neurosci. 2023 Mar 14:15:1120615. doi: 10.3389/fnagi.2023.1120615. eCollection 2023.

Authors

Qi Wu^{1

2}, Shulin Liu¹, Xiurong Huang¹, Jiabin Liu¹, Yige Wang¹, Yaqing Xiang¹, Xuxiong Tang^{1

2}, Qian Xu^{1

2

3

4

5

6}, Xinxiang Yan^{1

2

3

5

6}, Beisha Tang^{1

2

3

5

6}, Jifeng Guo^{1

2

3

4

5

6}

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China.
³ Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China.
⁴ Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
⁵ Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China.
⁶ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Introduction: 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.

Methods: 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.

Results: 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, p = 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.

Discussion: 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.

Keywords: Mendelian randomization; Parkinson’s disease; causal relationship; genome-wide association studies; psychiatric disorders.