Polygenic determinants of Parkinson's disease in a Chinese population

Guo, Jifeng; Li, Kai; Yu, Ri-li; Sun, Qi-Yin; Wang, Lei; Yao, Lingyan; Hu, Yacen; Lv, Zhanyun; Luo, Lin-zi; Shen, Lu; Jiang, Hong; Yan, Xinxiang; Pan, Qian; Xia, Kun; Tang, Beisha

doi:10.1016/j.neurobiolaging.2014.12.030

Cited by 43 publications

(23 citation statements)

References 32 publications

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“…All 1147 PD patients were detected for GBA gene L444P mutation, the most common PD-associated GBA mutation in Chinese population [ 24 ]. The screening procedures and details have been reported recently [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Effect ofGBAMutations on Phenotype of Parkinson’s Disease: A Study on Chinese Population and aMeta-Analysis

Zhang

Sun

Zhao

et al. 2015

Parkinson's Disease

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GBA has been identified as a genetic risk factor for PD. Whether the clinical manifestations of PD patients with or without GBA mutations are different has still not reached a consensus. We firstly detected the GBA mutation L444P in 1147 Chinese PD patients and simultaneously evaluated their corresponding clinical data. Then we compared the phenotypes between 646 PD patients with GBA mutations and 10344 PD patients without GBA mutations worldwide through meta-analysis. Through the method of meta-analysis, there was significant difference in age at onset (MD = −3.10 [95% CI: −4.88, −1.32]), bradykinesia as an initial symptom (OR = 1.49 [95% CI: 1.15, 1.94]), having family history (OR = 1.50 [95% CI: 1.18, 1.91]), and dementia (OR = 3.21 [95% CI: 1.97, 5.24]) during the comparison between PD patients with and without GBA mutations. While, in the aspect of tremor as an initial symptom (OR = 0.81 [95% CI: 0.64, 1.03]), the severity of motor symptoms such as H-Y (MD = 0.06 [95% CI: −0.06, 0.17]) and UPDRS-III (MD = 1.61 [95% CI: −0.65, 3.87]) and having dyskinesia (OR = 1.60 [95% CI: 0.90, 2.84]) during the comparison between the two groups revealed no statistical differences. Our results suggested that the phenotypes of PD patients with GBA mutations are different from GBA noncarriers.

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Section: Methodsmentioning

confidence: 99%

Effect ofGBAMutations on Phenotype of Parkinson’s Disease: A Study on Chinese Population and aMeta-Analysis

Zhang

Sun

Zhao

et al. 2015

Parkinson's Disease

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“…Although the etiology remains both complex and elusive, PD is currently acknowledged to be a multifactorial disorder related to genetic factors, aging, environmental exposures, epigenetic factors, and their synergistic interaction 1 4 11 12 . Genetic factors acting as disease-causing determinants, risk or protective factors, can contribute considerably to PD pathogenesis 4 7 13 . Over the last two decades, at least 23 genetic loci ( PARK1 to PARK23 ), and 18 disease-associated genes, have been implicated in familial and sporadic PD 14 15 16 17 .…”

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confidence: 99%

“…Approximately 10% of PD cases report a positive family history with the vast majority of cases having undefined genetic causes 4 7 18 . A polygenic model has been proposed to explain the genetic role in PD pathogenesis 13 . Even though the exact pathogenic mechanisms remain unclear, a complex and synergistic set of mitochondrial defects, and cellular processes including oxidative stress, lysosomal dysfunction, and vesicle trafficking are suggested to have a central role in PD pathogenesis 4 8 17 .…”

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confidence: 99%

Systematic analysis of genetic variants in Han Chinese patients with sporadic Parkinson’s disease

Yuan

Song

Deng

et al. 2016

Sci Rep

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Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. Accumulated evidence confirms that genetic factors play a considerable role in PD pathogenesis. To examine whether point variants or haplotypes are associated with PD development, genotyping of 35 variants in 22 PD-related genes was performed in a well-characterized cohort of 512 Han Chinese PD patients and 512 normal controls. Both Pearson’s χ2 test and haplotype analysis were used to evaluate whether variants or their haplotypes were associated with PD in this cohort. The only statistically significant differences in genotypic and allelic frequencies between the patients and the controls were in the DnaJ heat shock protein family (Hsp40) member C10 gene (DNAJC10) variant rs13414223 (P = 0.004 and 0.002, respectively; odds ratio = 0.652, 95% confidence interval: 0.496–0.857). No other variants or haplotypes exhibited any significant differences between these two groups (all corrected P > 0.05). Our findings indicate that the variant rs13414223 in the DNAJC10 gene, a paralog of PD-related genes DNAJC6 and DNAJC13, may play a protective role in PD. This suggests it may be a PD-associated gene.

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“…A meta‐analysis and genomewide association studies (GWAS) in different populations have affirmed that BST1 rs4698412 was relevant to the increased risk of sporadic PD. Particularly, a study in Chinese population also manifested the association between BST1 rs4698412 and PD . Taken together, these results prompted the potential role of BST1 rs4698412 allele in the development of PD.…”

Section: Introductionmentioning

confidence: 73%

“…Particularly, a study in Chinese population also manifested the association between BST1 rs4698412 and PD. 15 Taken together, these results prompted the potential role of BST1 rs4698412 allele in the development of PD.…”

mentioning

confidence: 91%

BST1 rs4698412 allelic variant increases the risk of gait or balance deficits in patients with Parkinson’s disease

Shen

Wang

et al. 2019

CNS Neurosci Ther

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Summary Aims We aimed to explore effects of bone marrow stromal cell antigen‐1 (BST1) rs4698412 allelic variant on brain activation and associative clinical symptoms in Parkinson’s disease (PD). Methods A total of 49 PD patients and 47 healthy control (HC) subjects were recruited for clinical evaluations, blood samples collection for genotypes, and resting‐state functional MRI (rs‐fMRI) scans. Based on BST1 rs4698412 allelic variant (G → A), participants were further divided into 18 PD‐GG, 31 PD‐GA/AA, 20 HC‐GG, and 27 HC‐GA/AA carriers, which respectively indicated subjects carrying ancestral or risk allele in that locus in PD or HC. Two‐way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions between PD and BST1 rs4698412 allelic variant on brain function via amplitude of low‐frequency fluctuations (ALFF). Spearman’s correlations were then utilized to detect associations between interactive brain regions and clinical symptoms. Results Compared to HC subjects, PD patients exhibited increased ALFF values in left cerebellum_8 and cerebellum_9. Significant interaction was in right lingual gyrus, where there were the lowest ALFF values and ALFF values were only negatively associated with Timed Up and Go (TUG) test time in PD‐GA/AA subgroup. Conclusion BST1 rs4698412‐modulated lingual gyrus functional alterations could be related to gait and balance dysfunction in PD.

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Polygenic determinants of Parkinson's disease in a Chinese population

Cited by 43 publications

References 32 publications

Effect ofGBAMutations on Phenotype of Parkinson’s Disease: A Study on Chinese Population and aMeta-Analysis

Effect ofGBAMutations on Phenotype of Parkinson’s Disease: A Study on Chinese Population and aMeta-Analysis

Systematic analysis of genetic variants in Han Chinese patients with sporadic Parkinson’s disease

BST1 rs4698412 allelic variant increases the risk of gait or balance deficits in patients with Parkinson’s disease

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