A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han Population
Immune thrombocytopenia (ITP) is an acquired bleeding disease due to immune-mediated destruction of antilogous platelets and ineffective thrombopoiesis. Although the etiology of ITP remains unknown, genetic variants are thought to predispose individuals to the disease. Several candidate gene analyse...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2020/7531876 |
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| author | Yanmei Xu Jing Li Wentao Yang Xiaoli Tang Bo Huang Jing Liu Jin Lin Jing Zhang Weiming Yang Shuqi Li Fan Sun Libin Deng Xiaozhong Wang |
| author_facet | Yanmei Xu Jing Li Wentao Yang Xiaoli Tang Bo Huang Jing Liu Jin Lin Jing Zhang Weiming Yang Shuqi Li Fan Sun Libin Deng Xiaozhong Wang |
| author_sort | Yanmei Xu |
| collection | DOAJ |
| description | Immune thrombocytopenia (ITP) is an acquired bleeding disease due to immune-mediated destruction of antilogous platelets and ineffective thrombopoiesis. Although the etiology of ITP remains unknown, genetic variants are thought to predispose individuals to the disease. Several candidate gene analyses have identified several loci that increased ITP susceptibility, but no systematic genetic analysis on a genome-wide scope. To extend the genetic evidence and to identify novel candidates of ITP, we performed a pooling genome-wide association study (GWAS) by IlluminaHumanOmniZhongHua-8 combining pathway analysis in 200 ITP cases and 200 controls from Chinese Han population (CHP). The results revealed that 4 novel loci (rs117503120, rs5998634, rs4483616, and rs16866133) were strongly associated with ITP (P<1.0×10−7). Expect for rs4483616, other three loci were validated by the TaqMan probe genotyping assay (P<0.05) in another cohort including 250 ITP cases and 250 controls. And rs5998634 T allele was more sensitive to glucocorticoids for ITP patients (χ2=7.30, P<0.05). Moreover, we identified three overrepresented signaling pathways including the neuroactive ligand-receptor interaction, pathways in cancer, and the JAK-STAT pathway, which involved in the etiology of ITP. In conclusion, our results revealed four novel loci and three pathways related to ITP and provided new clues to explore the pathogenesis of ITP. |
| format | Article |
| id | doaj-art-162108eecfc44e0189df64d0f9035732 |
| institution | Kabale University |
| issn | 2314-436X 2314-4378 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-162108eecfc44e0189df64d0f90357322025-02-03T06:43:50ZengWileyInternational Journal of Genomics2314-436X2314-43782020-01-01202010.1155/2020/75318767531876A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han PopulationYanmei Xu0Jing Li1Wentao Yang2Xiaoli Tang3Bo Huang4Jing Liu5Jin Lin6Jing Zhang7Weiming Yang8Shuqi Li9Fan Sun10Libin Deng11Xiaozhong Wang12Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Organ Transplantation, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaCollege of Basic Medical Science, Nanchang University, Nanchang 330031, ChinaDepartment of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaDepartment of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaCollege of Basic Medical Science, Nanchang University, Nanchang 330031, ChinaDepartment of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaImmune thrombocytopenia (ITP) is an acquired bleeding disease due to immune-mediated destruction of antilogous platelets and ineffective thrombopoiesis. Although the etiology of ITP remains unknown, genetic variants are thought to predispose individuals to the disease. Several candidate gene analyses have identified several loci that increased ITP susceptibility, but no systematic genetic analysis on a genome-wide scope. To extend the genetic evidence and to identify novel candidates of ITP, we performed a pooling genome-wide association study (GWAS) by IlluminaHumanOmniZhongHua-8 combining pathway analysis in 200 ITP cases and 200 controls from Chinese Han population (CHP). The results revealed that 4 novel loci (rs117503120, rs5998634, rs4483616, and rs16866133) were strongly associated with ITP (P<1.0×10−7). Expect for rs4483616, other three loci were validated by the TaqMan probe genotyping assay (P<0.05) in another cohort including 250 ITP cases and 250 controls. And rs5998634 T allele was more sensitive to glucocorticoids for ITP patients (χ2=7.30, P<0.05). Moreover, we identified three overrepresented signaling pathways including the neuroactive ligand-receptor interaction, pathways in cancer, and the JAK-STAT pathway, which involved in the etiology of ITP. In conclusion, our results revealed four novel loci and three pathways related to ITP and provided new clues to explore the pathogenesis of ITP.http://dx.doi.org/10.1155/2020/7531876 |
| spellingShingle | Yanmei Xu Jing Li Wentao Yang Xiaoli Tang Bo Huang Jing Liu Jin Lin Jing Zhang Weiming Yang Shuqi Li Fan Sun Libin Deng Xiaozhong Wang A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han Population International Journal of Genomics |
| title | A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han Population |
| title_full | A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han Population |
| title_fullStr | A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han Population |
| title_full_unstemmed | A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han Population |
| title_short | A Pooling Genome-Wide Association Study Identifies Susceptibility Loci and Signaling Pathways of Immune Thrombocytopenia in Chinese Han Population |
| title_sort | pooling genome wide association study identifies susceptibility loci and signaling pathways of immune thrombocytopenia in chinese han population |
| url | http://dx.doi.org/10.1155/2020/7531876 |
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