Phenome-wide association studies between SERINC2 and neuropsychiatric disorders
ObjectivesSERINC2 has been associated with alcoholism, bipolar disorder and autism, but the comparability and specificity issues of the findings remain unaddressed. The present study aimed to comprehensively analyze various neuropsychiatric disorders pinpoint the most reliable conditions predisposed...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1420395/full |
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| author | Ping Liu Xinqun Luo Liping Cao Yong Zhang Jiawu Ji Xiaoping Wang Kesheng Wang Xinghua Pan Ruilan Yang Zewen Tan Yunlong Tan Chiang-shan Li Xiaoyun Guo Zhiren Wang Xingguang Luo Xingguang Luo |
| author_facet | Ping Liu Xinqun Luo Liping Cao Yong Zhang Jiawu Ji Xiaoping Wang Kesheng Wang Xinghua Pan Ruilan Yang Zewen Tan Yunlong Tan Chiang-shan Li Xiaoyun Guo Zhiren Wang Xingguang Luo Xingguang Luo |
| author_sort | Ping Liu |
| collection | DOAJ |
| description | ObjectivesSERINC2 has been associated with alcoholism, bipolar disorder and autism, but the comparability and specificity issues of the findings remain unaddressed. The present study aimed to comprehensively analyze various neuropsychiatric disorders pinpoint the most reliable conditions predisposed by SERINC2.MethodsA total of 2,187 imputed SNPs across SERINC2 were examined in 1,167,439 subjects from 72 independent cohorts with 18 different neuropsychiatric disorders. SNP-disease associations were tested and then meta-analyzed, followed by FDR correction, to identify significant disease-risk SNPs. Finally, functional studies on the differential SERINC2 mRNA expression in brains and the potential regulatory effects of disease-risk alleles on SERINC2 mRNA expression, gray matter volumes (GMVs) of subcortical structures, cortical surface area (SA) and average thickness (TH) were conducted.ResultsIn European descent, alcoholism was most significantly associated with SERINC2 variants (245 SNPs with 5.5×10-8≤p ≤ 0.049 and 4.9×10-5≤q ≤ 0.034) that were largely shared across cocaine dependence, marijuana dependence, nicotine dependence, polysubstance dependence, schizophrenia, OCD, and autism (8.2×10-8≤p ≤ 0.050 and 1.9×10-5≤q ≤ 0.049); in Chinese population, bipolar disorder was also significantly associated with SERINC2 variants (10 SNPs: 1.3×10-4≤p ≤ 4.7×10-4 and 0.025≤q ≤ 0.031). Furthermore, the disease-risk alleles had highly similar regulatory effects on mRNA expression (8.1×10-7≤p ≤ 0.046), subcortical GMVs (7.0×10-4≤p ≤ 0.048) and cortical TH and SA (1.3×10-3≤p ≤ 0.050) in brains across alcoholism, schizophrenia, OCD and autism. The bipolar disorder-risk alleles had these regulatory effects but with different effect patterns. Finally, SERINC2 mRNA was differentially expressed in several brain regions between alcoholism or schizophrenia and controls.ConclusionSERINC2 is primarily linked to substance use disorders, schizophrenia, OCD, autism and bipolar disorder, not only statistically but also biologically. |
| format | Article |
| id | doaj-art-baa6d75da5a94e49bbe3ee957cd72670 |
| institution | Kabale University |
| issn | 1664-0640 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj-art-baa6d75da5a94e49bbe3ee957cd726702025-01-20T12:03:05ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-01-011510.3389/fpsyt.2024.14203951420395Phenome-wide association studies between SERINC2 and neuropsychiatric disordersPing Liu0Xinqun Luo1Liping Cao2Yong Zhang3Jiawu Ji4Xiaoping Wang5Kesheng Wang6Xinghua Pan7Ruilan Yang8Zewen Tan9Yunlong Tan10Chiang-shan Li11Xiaoyun Guo12Zhiren Wang13Xingguang Luo14Xingguang Luo15Department of Psychosomatic Medicine, People’s Hospital of Deyang City, Deyang, Sichuan, ChinaDepartment of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Psychiatry, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaInstitute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, ChinaDepartment of Psychiatry, Fujian Medical University Affiliated Fuzhou Neuropsychiatric Hospital, Fuzhou, Fujian, ChinaDepartment of Neurology, Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Biobehavioral Health and Nursing Science, College of Nursing, University of South Carolina, Columbia, SC, United StatesPrecision Regenerative Medicine Research Centre, Medical Science Division, and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, Macao SAR, ChinaDepartment of Psychiatry, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Psychiatry, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaBeijing Huilongguan Hospital, Peking University Huilongguan School of Clinical Medicine, Beijing, China0Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBeijing Huilongguan Hospital, Peking University Huilongguan School of Clinical Medicine, Beijing, ChinaBeijing Huilongguan Hospital, Peking University Huilongguan School of Clinical Medicine, Beijing, China0Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United StatesObjectivesSERINC2 has been associated with alcoholism, bipolar disorder and autism, but the comparability and specificity issues of the findings remain unaddressed. The present study aimed to comprehensively analyze various neuropsychiatric disorders pinpoint the most reliable conditions predisposed by SERINC2.MethodsA total of 2,187 imputed SNPs across SERINC2 were examined in 1,167,439 subjects from 72 independent cohorts with 18 different neuropsychiatric disorders. SNP-disease associations were tested and then meta-analyzed, followed by FDR correction, to identify significant disease-risk SNPs. Finally, functional studies on the differential SERINC2 mRNA expression in brains and the potential regulatory effects of disease-risk alleles on SERINC2 mRNA expression, gray matter volumes (GMVs) of subcortical structures, cortical surface area (SA) and average thickness (TH) were conducted.ResultsIn European descent, alcoholism was most significantly associated with SERINC2 variants (245 SNPs with 5.5×10-8≤p ≤ 0.049 and 4.9×10-5≤q ≤ 0.034) that were largely shared across cocaine dependence, marijuana dependence, nicotine dependence, polysubstance dependence, schizophrenia, OCD, and autism (8.2×10-8≤p ≤ 0.050 and 1.9×10-5≤q ≤ 0.049); in Chinese population, bipolar disorder was also significantly associated with SERINC2 variants (10 SNPs: 1.3×10-4≤p ≤ 4.7×10-4 and 0.025≤q ≤ 0.031). Furthermore, the disease-risk alleles had highly similar regulatory effects on mRNA expression (8.1×10-7≤p ≤ 0.046), subcortical GMVs (7.0×10-4≤p ≤ 0.048) and cortical TH and SA (1.3×10-3≤p ≤ 0.050) in brains across alcoholism, schizophrenia, OCD and autism. The bipolar disorder-risk alleles had these regulatory effects but with different effect patterns. Finally, SERINC2 mRNA was differentially expressed in several brain regions between alcoholism or schizophrenia and controls.ConclusionSERINC2 is primarily linked to substance use disorders, schizophrenia, OCD, autism and bipolar disorder, not only statistically but also biologically.https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1420395/fullSERINC2phenomealcoholismschizophreniaOCDautism |
| spellingShingle | Ping Liu Xinqun Luo Liping Cao Yong Zhang Jiawu Ji Xiaoping Wang Kesheng Wang Xinghua Pan Ruilan Yang Zewen Tan Yunlong Tan Chiang-shan Li Xiaoyun Guo Zhiren Wang Xingguang Luo Xingguang Luo Phenome-wide association studies between SERINC2 and neuropsychiatric disorders Frontiers in Psychiatry SERINC2 phenome alcoholism schizophrenia OCD autism |
| title | Phenome-wide association studies between SERINC2 and neuropsychiatric disorders |
| title_full | Phenome-wide association studies between SERINC2 and neuropsychiatric disorders |
| title_fullStr | Phenome-wide association studies between SERINC2 and neuropsychiatric disorders |
| title_full_unstemmed | Phenome-wide association studies between SERINC2 and neuropsychiatric disorders |
| title_short | Phenome-wide association studies between SERINC2 and neuropsychiatric disorders |
| title_sort | phenome wide association studies between serinc2 and neuropsychiatric disorders |
| topic | SERINC2 phenome alcoholism schizophrenia OCD autism |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1420395/full |
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