Volume 37, Issue 12 p. 2451-2456
Brief Report

Mendelian Randomization Study Using Dopaminergic Neuron-Specific eQTL Nominates Potential Causal Genes for Parkinson's Disease

Xinglun Dang MSc

Xinglun Dang MSc

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China

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Zhijun Zhang MD, PhD

Corresponding Author

Zhijun Zhang MD, PhD

Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, China

Department of Neurology, Affiliated Zhongda Hospital, Institution of Neuropsychiatry, Southeast University, Nanjing, China

Department of Mental Health and Public Health, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Correspondence to: Drs. Zhijun Zhang and Xiong-Jian Luo, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, Jiangsu, 210096, China; E-mail: [email protected] and [email protected]

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Xiong-Jian Luo PhD

Corresponding Author

Xiong-Jian Luo PhD

Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, China

Department of Neurology, Affiliated Zhongda Hospital, Institution of Neuropsychiatry, Southeast University, Nanjing, China

Correspondence to: Drs. Zhijun Zhang and Xiong-Jian Luo, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, Jiangsu, 210096, China; E-mail: [email protected] and [email protected]

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First published: 29 September 2022
Citations: 2

Abstract

Background

Large-scale genome-wide association studies (GWASs) have reported multiple risk variants for Parkinson's disease (PD). However, little is known about how these reported risk variants confer risk of PD.

Objective

To nominate genes whose genetically regulated expression in dopaminergic neurons may have a causal role in PD.

Methods

We conducted a two-sample Mendelian randomization (MR) study by integrating large-scale genome-wide associations and expression quantitative trait loci (eQTL) data from dopaminergic neurons.

Results

MR analysis nominated 10 risk genes whose genetically regulated expression in dopaminergic neurons may have a causal role in PD. These MR significant genes include FAM200B, NDUFAF2, NUP42, SH3GL2, STX1B, CCDC189, KAT8, PRSS36, VAMP4, and ZSWIM7.

Conclusions

We report the first MR study of PD by using dopaminergic neuron-specific eQTL and nominate novel risk genes for PD. Further functional characterization of the nominated risk genes will provide mechanistic insights into PD pathogenesis and potential therapeutic targets. © 2022 International Parkinson and Movement Disorder Society.

Data Availability Statement

Genome-wide associations of PD were from the study of Nalls et al.2 eQTL of dopaminergic neurons were from the study of Jerber et al.7 Other results from this study are provided in the Supplementary material. The code used for the analysis can be found on Github (https://github.com/Dangxl/PD-cell-type-MR).