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

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机构: [1]Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Kunming, Yunnan, Peoples R China [2]Southeast Univ, Zhongda Hosp, Sch Life Sci & Technol, Adv Inst Life & Hlth, Nanjing 210096, Jiangsu, Peoples R China [3]Southeast Univ, Affiliated Zhongda Hosp, Inst Neuropsychiat, Dept Neurol, Nanjing, Peoples R China [4]Chinese Acad Sci, Fac Life & Hlth Sci, Shenzhen Inst Adv Technol, Dept Mental Hlth & Publ Hlth, Shenzhen, Peoples R China
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关键词: Parkinson's disease genome-wide association studies expression quantitative trait loci Mendelian randomization dopaminergic neurons

摘要:
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. (c) 2022 International Parkinson and Movement Disorder Society.

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大类 | 1 区 医学
小类 | 1 区 临床神经病学
最新[2023]版:
大类 | 1 区 医学
小类 | 2 区 临床神经病学
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Q1 CLINICAL NEUROLOGY
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Q1 CLINICAL NEUROLOGY

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第一作者机构: [1]Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Kunming, Yunnan, Peoples R China
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通讯机构: [2]Southeast Univ, Zhongda Hosp, Sch Life Sci & Technol, Adv Inst Life & Hlth, Nanjing 210096, Jiangsu, Peoples R China [3]Southeast Univ, Affiliated Zhongda Hosp, Inst Neuropsychiat, Dept Neurol, Nanjing, Peoples R China [4]Chinese Acad Sci, Fac Life & Hlth Sci, Shenzhen Inst Adv Technol, Dept Mental Hlth & Publ Hlth, Shenzhen, Peoples R China [*1]Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, Jiangsu, 210096, China
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