Investigating the shared genetic architecture between schizophrenia and sex hormone traits
Abstract Sex hormones are involved in schizophrenia pathogenesis; however, their direction and genetic overlap remain unknown. By leveraging summary statistics from large-scale genome-wide association studies, we quantified the shared genetic architecture between schizophrenia and four sex hormone t...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-03-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03305-7 |
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| author | Xiaoyan He Qingyan Ma Jing Liu Pu Lei Huan Peng Wen Lu Yixin Liu Xianyan Zhan Bin Yan Xiancang Ma Jian Yang |
| author_facet | Xiaoyan He Qingyan Ma Jing Liu Pu Lei Huan Peng Wen Lu Yixin Liu Xianyan Zhan Bin Yan Xiancang Ma Jian Yang |
| author_sort | Xiaoyan He |
| collection | DOAJ |
| description | Abstract Sex hormones are involved in schizophrenia pathogenesis; however, their direction and genetic overlap remain unknown. By leveraging summary statistics from large-scale genome-wide association studies, we quantified the shared genetic architecture between schizophrenia and four sex hormone traits. Linkage disequilibrium score regression and bivariate causal mixture modeling strategies showed significant positive correlations between sex hormone-binding globulin (SHBG), total testosterone, and schizophrenia, while bioavailable testosterone and schizophrenia were negatively correlated. Estradiol showed a weak positive correlation with schizophrenia, with little polygenic overlap. The conjunctional false discovery rate method identified 303 lead single-nucleotide polymorphisms (SNPs) in jointly shared genomic loci between schizophrenia and SHBG, with 130, 52, and 9 SNPs shared between schizophrenia and total testosterone, bioavailable testosterone, and estradiol, respectively. Functional annotation suggests that mitotic sister chromatid segregation and N-glycan biosynthesis may be involved in common mechanisms underlying sex hormone regulation and schizophrenia onset. In conclusion, this study clarified the inherent relationships between schizophrenia and sex hormone traits, highlighted the roles of mitotic sister chromatid segregation and N-glycan biosynthesis in the pathogenesis of schizophrenia, and delivered potential targets for further validation. |
| format | Article |
| id | doaj-art-5fc3ceef3b0a44a0b8d1d6ba74964123 |
| institution | DOAJ |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-5fc3ceef3b0a44a0b8d1d6ba749641232025-08-20T02:52:19ZengNature Publishing GroupTranslational Psychiatry2158-31882025-03-011511810.1038/s41398-025-03305-7Investigating the shared genetic architecture between schizophrenia and sex hormone traitsXiaoyan He0Qingyan Ma1Jing Liu2Pu Lei3Huan Peng4Wen Lu5Yixin Liu6Xianyan Zhan7Bin Yan8Xiancang Ma9Jian Yang10Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityCenter for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Psychiatry, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Sex hormones are involved in schizophrenia pathogenesis; however, their direction and genetic overlap remain unknown. By leveraging summary statistics from large-scale genome-wide association studies, we quantified the shared genetic architecture between schizophrenia and four sex hormone traits. Linkage disequilibrium score regression and bivariate causal mixture modeling strategies showed significant positive correlations between sex hormone-binding globulin (SHBG), total testosterone, and schizophrenia, while bioavailable testosterone and schizophrenia were negatively correlated. Estradiol showed a weak positive correlation with schizophrenia, with little polygenic overlap. The conjunctional false discovery rate method identified 303 lead single-nucleotide polymorphisms (SNPs) in jointly shared genomic loci between schizophrenia and SHBG, with 130, 52, and 9 SNPs shared between schizophrenia and total testosterone, bioavailable testosterone, and estradiol, respectively. Functional annotation suggests that mitotic sister chromatid segregation and N-glycan biosynthesis may be involved in common mechanisms underlying sex hormone regulation and schizophrenia onset. In conclusion, this study clarified the inherent relationships between schizophrenia and sex hormone traits, highlighted the roles of mitotic sister chromatid segregation and N-glycan biosynthesis in the pathogenesis of schizophrenia, and delivered potential targets for further validation.https://doi.org/10.1038/s41398-025-03305-7 |
| spellingShingle | Xiaoyan He Qingyan Ma Jing Liu Pu Lei Huan Peng Wen Lu Yixin Liu Xianyan Zhan Bin Yan Xiancang Ma Jian Yang Investigating the shared genetic architecture between schizophrenia and sex hormone traits Translational Psychiatry |
| title | Investigating the shared genetic architecture between schizophrenia and sex hormone traits |
| title_full | Investigating the shared genetic architecture between schizophrenia and sex hormone traits |
| title_fullStr | Investigating the shared genetic architecture between schizophrenia and sex hormone traits |
| title_full_unstemmed | Investigating the shared genetic architecture between schizophrenia and sex hormone traits |
| title_short | Investigating the shared genetic architecture between schizophrenia and sex hormone traits |
| title_sort | investigating the shared genetic architecture between schizophrenia and sex hormone traits |
| url | https://doi.org/10.1038/s41398-025-03305-7 |
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