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Exploring the Effects of Genetic Variants on Clinical Profiles of Parkinson's Disease Assessed by the Unified Parkinson's Disease Rating Scale and the Hoehn-Yahr Stage

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机构： [1]Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China, [2]Bioinformatics Center, School of Biomedical Engineering, Capital Medical University, Beijing, China, [3]Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China, [4]Department of Statistics, Purdue University, West Lafayette, Indiana, United States of America, [5]Department of Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China, [6]Key Laboratory on Neurodegenerative Disease of Ministry of Education and Key Laboratory on Parkinson’s Disease of Beijing, Beijing, China, [7]Department of Neurology, The Affiliated Sanming First Hospital of Fujian Medical University, Sanming, Fujian, China, [8]Parkinson Disease Center of Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China, [9]Alzheimer Disease Center of Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China

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Many genetic variants have been linked to familial or sporadic Parkinson's disease (PD), among which those identified in PARK16, BST1, SNCA, LRRK2, GBA and MAPT genes have been demonstrated to be the most common risk factors worldwide. Moreover, complex gene-gene and gene-environment interactions have been highlighted in PD pathogenesis. Compared to studies focusing on the predisposing effects of genes, there is a relative lack of research investigating how these genes and their interactions influence the clinical profiles of PD. In a cohort consisting of 2,011 Chinese Han PD patients, we selected 9 representative variants from the 6 above-mentioned common PD genes to analyze their main and epistatic effects on the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H-Y) stage of PD. With multiple linear regression models adjusting for medication status, disease duration, gender and age at onset, none of the variants displayed significant main effects on UPDRS or the H-Y scores. However, for gene-gene interaction analyses, 7 out of 37 pairs of variants showed significant or marginally significant associations with these scores. Among these, the GBA rs421016 (L444P)xLRRK2 rs33949390 (R1628P) interaction was consistently significant in relation to UPDRS III and UPDRS total (I+II+III), even after controlling for the family-wise error rate using False Discovery Rate (FDR-corrected p values are 0.0481 and 0.0070, respectively). Although the effects of the remaining pairs of variants did not survive the FDR correction, they showed marginally significant associations with either UPDRS or the H-Y stage (raw p<0.05). Our results highlight the importance of epistatic effects of multiple genes on the determination of PD clinical profiles and may have implications for molecular classification and personalized intervention of the disease.

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出版当年[2015]版：

大类 | 3 区生物

小类 | 3 区综合性期刊

最新[2023]版：

大类 | 3 区综合性期刊

小类 | 3 区综合性期刊

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出版当年[2014]版：

Q1 MULTIDISCIPLINARY SCIENCES

最新[2023]版：

Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 2.9 最新[2023版] 3.3 最新五年平均 3.234 出版当年[2014版] 3.702 出版当年五年平均 3.534 出版前一年[2013版] 3.057 出版后一年[2015版]

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第一作者机构： [1]Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China, [2]Bioinformatics Center, School of Biomedical Engineering, Capital Medical University, Beijing, China,

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通讯作者：

通讯机构： [1]Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China, [2]Bioinformatics Center, School of Biomedical Engineering, Capital Medical University, Beijing, China, [3]Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China, [4]Department of Statistics, Purdue University, West Lafayette, Indiana, United States of America, [5]Department of Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China, [6]Key Laboratory on Neurodegenerative Disease of Ministry of Education and Key Laboratory on Parkinson’s Disease of Beijing, Beijing, China, [8]Parkinson Disease Center of Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China, [9]Alzheimer Disease Center of Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China

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