Integrated Genetic Analysis of Racial Differences of Common GBA Variants in Parkinson's Disease: A Meta-Analysis
Background: Numerous studies have indicated that there is a possible relationship between GBA variants and Parkinson's disease (PD), however, most of them focused on a few variants such as L444P, N370S. We performed a comprehensive pooled analysis to clarify the relationship between variations...
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00043/full |
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| author | Yuan Zhang Li Shu Qiying Sun Qiying Sun Qiying Sun Xun Zhou Hongxu Pan Jifeng Guo Jifeng Guo Jifeng Guo Beisha Tang Beisha Tang Beisha Tang Beisha Tang Beisha Tang |
| author_facet | Yuan Zhang Li Shu Qiying Sun Qiying Sun Qiying Sun Xun Zhou Hongxu Pan Jifeng Guo Jifeng Guo Jifeng Guo Beisha Tang Beisha Tang Beisha Tang Beisha Tang Beisha Tang |
| author_sort | Yuan Zhang |
| collection | DOAJ |
| description | Background: Numerous studies have indicated that there is a possible relationship between GBA variants and Parkinson's disease (PD), however, most of them focused on a few variants such as L444P, N370S. We performed a comprehensive pooled analysis to clarify the relationship between variations of GBA and the risk of PD in different racial groups.Methods: Standard meta-analysis was conducted, including generating inclusion and exclusion criteria, searching literature, extracting and analyzing data.Results: Fifty studies containing 20,267 PD patients and 24,807 controls were included. We found that variants 84insGG, IVS2+1G>A, R120W, H255Q, E326K, T369M, N370S, D409H, L444P, R496H and RecNciI increased the risk of PD in total populations (OR: 1.78–10.49; p: <0.00001, 0.00005, 0.0008, 0.005, <0.00001, 0.004, <0.00001, 0.0003, <0.00001, <0.0001, 0.0001). In subgroup analysis by ethnicity, in AJ populations, variants 84insGG, R496H, N370S increased the risk of PD (OR: 9.26–3.51; p: <0.00001, <0.0001, <0.00001). In total non-AJ populations, variants L444P, R120W, IVS2+1G>A, H255Q, N370S, D409H, RecNciI, E326K, T369M increased the risk of PD (OR: 8.66–1.89; p: <0.00001, 0.0008, 0.02, 0.005, <0.00001, 0.001, 0.0001, <0.00001, 0.002). Among the non-AJ populations, pooled analysis from five different groups were done separately. Variants L444P, N370S, H255Q, D409H, RecNciI, E326K increased risk of PD (OR: 6.52–1.84; p: <0.00001, <0.00001, 0.005, 0.005, 0.04, <0.00001) in European/West Asians while R120W and RecNciI in East Asians (OR: 14.93, 3.56; p: 0.001, 0.003). L444P increased the risk of PD in Hispanics, East Asians and Mixed populations (OR: 15.44, 12.43, 7.33; p: 0.00004, <0.00001, 0.009). Lacking of enough original studies, we failed to conduct quantitative analysis in Africa.Conclusions: Obvious racial differences were found for GBA variants in PD. 84insGG and R496H exclusively increased PD risks in AJ populations, so did L444P, R120W, IVS2+1G>A, H255Q, D409H, RecNciI, E326K, T369M in non-AJ populations. N370S increased the risk of PD in both ethnics. In non-AJ subgroup populations, N370S, H255Q, D409H, E326K exclusively increased PD risks in European/West Asians, as were R120W in East Asians. L444P increased the risk of PD in all groups in non-AJ ethnicity. These results will contribute to the future genetic screening of GBA gene in PD. |
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| last_indexed | 2024-12-23T06:15:38Z |
| publishDate | 2018-02-01 |
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| spelling | doaj.art-e18e49b4045a47199fe3a9cc8b7e42ab2022-12-21T17:57:19ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-02-011110.3389/fnmol.2018.00043327820Integrated Genetic Analysis of Racial Differences of Common GBA Variants in Parkinson's Disease: A Meta-AnalysisYuan Zhang0Li Shu1Qiying Sun2Qiying Sun3Qiying Sun4Xun Zhou5Hongxu Pan6Jifeng Guo7Jifeng Guo8Jifeng Guo9Beisha Tang10Beisha Tang11Beisha Tang12Beisha Tang13Beisha Tang14Department of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaKey Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaKey Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaKey Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, ChinaCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaParkinson's Disease Center of Beijing Institute for Brain Disorders, Beijing, ChinaBackground: Numerous studies have indicated that there is a possible relationship between GBA variants and Parkinson's disease (PD), however, most of them focused on a few variants such as L444P, N370S. We performed a comprehensive pooled analysis to clarify the relationship between variations of GBA and the risk of PD in different racial groups.Methods: Standard meta-analysis was conducted, including generating inclusion and exclusion criteria, searching literature, extracting and analyzing data.Results: Fifty studies containing 20,267 PD patients and 24,807 controls were included. We found that variants 84insGG, IVS2+1G>A, R120W, H255Q, E326K, T369M, N370S, D409H, L444P, R496H and RecNciI increased the risk of PD in total populations (OR: 1.78–10.49; p: <0.00001, 0.00005, 0.0008, 0.005, <0.00001, 0.004, <0.00001, 0.0003, <0.00001, <0.0001, 0.0001). In subgroup analysis by ethnicity, in AJ populations, variants 84insGG, R496H, N370S increased the risk of PD (OR: 9.26–3.51; p: <0.00001, <0.0001, <0.00001). In total non-AJ populations, variants L444P, R120W, IVS2+1G>A, H255Q, N370S, D409H, RecNciI, E326K, T369M increased the risk of PD (OR: 8.66–1.89; p: <0.00001, 0.0008, 0.02, 0.005, <0.00001, 0.001, 0.0001, <0.00001, 0.002). Among the non-AJ populations, pooled analysis from five different groups were done separately. Variants L444P, N370S, H255Q, D409H, RecNciI, E326K increased risk of PD (OR: 6.52–1.84; p: <0.00001, <0.00001, 0.005, 0.005, 0.04, <0.00001) in European/West Asians while R120W and RecNciI in East Asians (OR: 14.93, 3.56; p: 0.001, 0.003). L444P increased the risk of PD in Hispanics, East Asians and Mixed populations (OR: 15.44, 12.43, 7.33; p: 0.00004, <0.00001, 0.009). Lacking of enough original studies, we failed to conduct quantitative analysis in Africa.Conclusions: Obvious racial differences were found for GBA variants in PD. 84insGG and R496H exclusively increased PD risks in AJ populations, so did L444P, R120W, IVS2+1G>A, H255Q, D409H, RecNciI, E326K, T369M in non-AJ populations. N370S increased the risk of PD in both ethnics. In non-AJ subgroup populations, N370S, H255Q, D409H, E326K exclusively increased PD risks in European/West Asians, as were R120W in East Asians. L444P increased the risk of PD in all groups in non-AJ ethnicity. These results will contribute to the future genetic screening of GBA gene in PD.http://journal.frontiersin.org/article/10.3389/fnmol.2018.00043/fullParkinson's diseaseGBAAJnon-AJmeta-analysis |
| spellingShingle | Yuan Zhang Li Shu Qiying Sun Qiying Sun Qiying Sun Xun Zhou Hongxu Pan Jifeng Guo Jifeng Guo Jifeng Guo Beisha Tang Beisha Tang Beisha Tang Beisha Tang Beisha Tang Integrated Genetic Analysis of Racial Differences of Common GBA Variants in Parkinson's Disease: A Meta-Analysis Frontiers in Molecular Neuroscience Parkinson's disease GBA AJ non-AJ meta-analysis |
| title | Integrated Genetic Analysis of Racial Differences of Common GBA Variants in Parkinson's Disease: A Meta-Analysis |
| title_full | Integrated Genetic Analysis of Racial Differences of Common GBA Variants in Parkinson's Disease: A Meta-Analysis |
| title_fullStr | Integrated Genetic Analysis of Racial Differences of Common GBA Variants in Parkinson's Disease: A Meta-Analysis |
| title_full_unstemmed | Integrated Genetic Analysis of Racial Differences of Common GBA Variants in Parkinson's Disease: A Meta-Analysis |
| title_short | Integrated Genetic Analysis of Racial Differences of Common GBA Variants in Parkinson's Disease: A Meta-Analysis |
| title_sort | integrated genetic analysis of racial differences of common gba variants in parkinson s disease a meta analysis |
| topic | Parkinson's disease GBA AJ non-AJ meta-analysis |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00043/full |
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