Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson's diseaseOA北大核心CSTPCDMEDLINE
Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson's disease
Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson's disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been undertaken.Therefore,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD. Methods:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls.Additionally,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls. Results:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,respectively.Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD.However,the significance did not pass the Bonferroni correction.Meanwhile,72 and 1730 common variants were found in the WES and WGS cohorts,respectively.Unfortunately,single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients.However,we highlight the complexity of PD and the need for extensive research elucidating its etiology.
Yuwen Zhao;Qiying Sun;Jifeng Guo;Xinxiang Yan;Beisha Tang;Qian Xu;Lixia Qin;Hongxu Pan;Tingwei Song;Yige Wang;Xiaoxia Zhou;Yaqin Xiang;Jinchen Li;Zhenhua Liu
Department of Neurology,Xiangya Hospital,Central South University,Changsha,Hunan 410008,ChinaDepartment of Geriatrics,Xiangya Hospital,Central South University,Changsha,Hunan 410008,ChinaDepartment of Neurology,Xiangya Hospital,Central South University,Changsha,Hunan 410008,China||Bioinformatics Center National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha,Hunan 410008,China||Centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics,School of Life Sciences,Central South University,Changsha,Hunan 410008,China||Key Laboratory of Hunan Province in Neurodegenerative Disorders,Central South University,Changsha,Hunan 410008,ChinaDepartment of Neurology,The Second Xiangya Hospital,Central South University,Changsha,Hunan 410011,ChinaBioinformatics Center National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha,Hunan 410008,China||Department of Geriatrics,Xiangya Hospital,Central South University,Changsha,Hunan 410008,China||Centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics,School of Life Sciences,Central South University,Changsha,Hunan 410008,China
Parkinson's diseaseTranscription factorsDopaminergic neuronsGeneticVariants
《中华医学杂志（英文版）》 2024 (004)
450-456 / 7
This work was supported by grants from the National Natural Science Foundation of China(Nos.82071437,U20A20355,and 82101342),the Hunan Innovative Province Construction Project(No.2019SK2335),the Natural Science Foundations of Hunan Province(No.2021JJ31115),the National Key Research and Development Program of China(Nos.2016YFC1306000 and 2021YFC2502100),and the Project Program of National Clinical Research Center for Geriatric Disorders(Xiangya Hospital)(No.2021KFJJ10).
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