Association study of the complement component C4 gene and suicide risk in schizophrenia
Abstract Schizophrenia is a severe mental illness and a major risk factor for suicide, with approximately 50% of schizophrenia patients attempting and 10% dying from suicide. Although genetic components play a significant role in schizophrenia risk, the underlying genetic risk factors for suicide ar...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-024-00440-w |
| _version_ | 1797274271745048576 |
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| author | Mahbod Ebrahimi Kowsar Teymouri Cheng C. Chen Ayeshah G. Mohiuddin Jennie G. Pouget Vanessa F. Goncalves Arun K. Tiwari Clement C. Zai James L. Kennedy |
| author_facet | Mahbod Ebrahimi Kowsar Teymouri Cheng C. Chen Ayeshah G. Mohiuddin Jennie G. Pouget Vanessa F. Goncalves Arun K. Tiwari Clement C. Zai James L. Kennedy |
| author_sort | Mahbod Ebrahimi |
| collection | DOAJ |
| description | Abstract Schizophrenia is a severe mental illness and a major risk factor for suicide, with approximately 50% of schizophrenia patients attempting and 10% dying from suicide. Although genetic components play a significant role in schizophrenia risk, the underlying genetic risk factors for suicide are poorly understood. The complement component C4 gene, an immune gene involved in the innate immune system and located in the major histocompatibility complex (MHC) region, has been identified to be strongly associated with schizophrenia risk. In addition, recent findings have also suggested that the MHC region has been associated with suicide risk across disorders, making C4 a potential candidate of interest for studying suicidality in schizophrenia patients. Despite growing interest in investigating the association between the C4 gene and schizophrenia, to our knowledge, no work has been done to examine the potential of C4 variants as suicide risk factors in patients with schizophrenia. In this study, we investigated the association between different C4 copy number variants and predicted C4 brain expression with suicidal outcomes (suicide attempts/suicidal ideation). We directly genotyped 434 schizophrenia patients to determine their C4A and C4B copy number variants. We found the C4AS copy number to be marginally and negatively associated with suicide risk, potentially being protective against suicide attempts (OR = 0.49; p = 0.05) and suicidal ideation (OR = 0.65; p = 0.07). Furthermore, sex-stratified analyses revealed that there are no significant differences between males and females. Our preliminary findings encourage additional studies of C4 and potential immune dysregulation in suicide. |
| first_indexed | 2024-03-07T14:57:03Z |
| format | Article |
| id | doaj.art-fa91f42a67434a70979e8d00c0942ab5 |
| institution | Directory Open Access Journal |
| issn | 2754-6993 |
| language | English |
| last_indexed | 2024-03-07T14:57:03Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Schizophrenia |
| spelling | doaj.art-fa91f42a67434a70979e8d00c0942ab52024-03-05T19:25:30ZengNature PortfolioSchizophrenia2754-69932024-02-011011910.1038/s41537-024-00440-wAssociation study of the complement component C4 gene and suicide risk in schizophreniaMahbod Ebrahimi0Kowsar Teymouri1Cheng C. Chen2Ayeshah G. Mohiuddin3Jennie G. Pouget4Vanessa F. Goncalves5Arun K. Tiwari6Clement C. Zai7James L. Kennedy8Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthTanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthAbstract Schizophrenia is a severe mental illness and a major risk factor for suicide, with approximately 50% of schizophrenia patients attempting and 10% dying from suicide. Although genetic components play a significant role in schizophrenia risk, the underlying genetic risk factors for suicide are poorly understood. The complement component C4 gene, an immune gene involved in the innate immune system and located in the major histocompatibility complex (MHC) region, has been identified to be strongly associated with schizophrenia risk. In addition, recent findings have also suggested that the MHC region has been associated with suicide risk across disorders, making C4 a potential candidate of interest for studying suicidality in schizophrenia patients. Despite growing interest in investigating the association between the C4 gene and schizophrenia, to our knowledge, no work has been done to examine the potential of C4 variants as suicide risk factors in patients with schizophrenia. In this study, we investigated the association between different C4 copy number variants and predicted C4 brain expression with suicidal outcomes (suicide attempts/suicidal ideation). We directly genotyped 434 schizophrenia patients to determine their C4A and C4B copy number variants. We found the C4AS copy number to be marginally and negatively associated with suicide risk, potentially being protective against suicide attempts (OR = 0.49; p = 0.05) and suicidal ideation (OR = 0.65; p = 0.07). Furthermore, sex-stratified analyses revealed that there are no significant differences between males and females. Our preliminary findings encourage additional studies of C4 and potential immune dysregulation in suicide.https://doi.org/10.1038/s41537-024-00440-w |
| spellingShingle | Mahbod Ebrahimi Kowsar Teymouri Cheng C. Chen Ayeshah G. Mohiuddin Jennie G. Pouget Vanessa F. Goncalves Arun K. Tiwari Clement C. Zai James L. Kennedy Association study of the complement component C4 gene and suicide risk in schizophrenia Schizophrenia |
| title | Association study of the complement component C4 gene and suicide risk in schizophrenia |
| title_full | Association study of the complement component C4 gene and suicide risk in schizophrenia |
| title_fullStr | Association study of the complement component C4 gene and suicide risk in schizophrenia |
| title_full_unstemmed | Association study of the complement component C4 gene and suicide risk in schizophrenia |
| title_short | Association study of the complement component C4 gene and suicide risk in schizophrenia |
| title_sort | association study of the complement component c4 gene and suicide risk in schizophrenia |
| url | https://doi.org/10.1038/s41537-024-00440-w |
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