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.
Keywords: Mendelian randomization; Parkinson's disease; dopaminergic neurons; expression quantitative trait loci; genome-wide association studies.
© 2022 International Parkinson and Movement Disorder Society.