孟德尔随机化
多巴胺能
表达数量性状基因座
帕金森病
LRRK2
遗传学
生物
全基因组关联研究
疾病
遗传关联
孟德尔遗传
基因
神经科学
医学
单核苷酸多态性
多巴胺
内科学
突变
基因型
遗传变异
作者
Xinglun Dang,Zhijun Zhang,Xiong‐Jian Luo
摘要
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.
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