Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases
Abstract The high comorbidity of major depressive disorder (MDD) with other diseases has been well-documented. However, the pairwise causal connections for MDD comorbid networks are poorly characterized. We performed Phenome-wide Mendelian randomization (MR) analyses to explore bidirectional causal...
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Nature Publishing Group
2024-12-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-024-03216-z |
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| author | Wenxi Sun Ancha Baranova Dongming Liu Hongbao Cao Xiaobin Zhang Fuquan Zhang |
| author_facet | Wenxi Sun Ancha Baranova Dongming Liu Hongbao Cao Xiaobin Zhang Fuquan Zhang |
| author_sort | Wenxi Sun |
| collection | DOAJ |
| description | Abstract The high comorbidity of major depressive disorder (MDD) with other diseases has been well-documented. However, the pairwise causal connections for MDD comorbid networks are poorly characterized. We performed Phenome-wide Mendelian randomization (MR) analyses to explore bidirectional causal associations between MDD (N = 807,553) and 877 common diseases from FinnGen datasets (N = 377,277). The inverse variance weighting method was the primary technique, and other methods (weighted median and MR-Egger) were used for sensitivity analyses. Our MR analyses showed that the genetic liability to MDD is causally associated with the risks of 324 disease phenotypes (average b: 0.339), including 46 psychiatric and behavioral disorders (average b: 0.618), 18 neurological diseases (average b: 0.348), 44 respiratory diseases (average b: 0.345), 40 digestive diseases (average b: 0.281), 18 circulatory diseases (average b: 0.237), 37 genitourinary diseases (average b: 0.271), 66 musculoskeletal and connective diseases (average b: 0.326), 22 endocrine diseases (average b: 0.302), and others. In a reverse analysis, a total of 51 genetic components predisposing to various diseases were causally associated with MDD risk (average b: 0.086), including 5 infectious diseases (average b: 0.056), 11 neurological diseases (average b: 0.106), 14 oncological diseases (average b: 0.108), and 5 psychiatric and behavioral disorders (average b: 0.114). Bidirectional causal associations were identified between MDD and 15 diseases. For most MR analyses, little evidence of heterogeneity and pleiotropy was detected. Our findings confirmed the extensive and significant causal role of genetic predisposition to MDD in contributing to human disease phenotypes, which were more pronounced than those seen in the reverse analysis of the causal influences of other diseases on MDD. |
| format | Article |
| id | doaj-art-fbad6b345f7d4b10ae5d5880a4faad88 |
| institution | Kabale University |
| issn | 2158-3188 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-fbad6b345f7d4b10ae5d5880a4faad882024-12-29T12:48:21ZengNature Publishing GroupTranslational Psychiatry2158-31882024-12-0114111210.1038/s41398-024-03216-zPhenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseasesWenxi Sun0Ancha Baranova1Dongming Liu2Hongbao Cao3Xiaobin Zhang4Fuquan Zhang5Suzhou Guangji Hospital, Suzhou, Jiangsu Province; Affiliated Guangji Hospital of Soochow UniversitySchool of Systems Biology, George Mason UniversityDepartment of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversitySchool of Systems Biology, George Mason UniversitySuzhou Guangji Hospital, Suzhou, Jiangsu Province; Affiliated Guangji Hospital of Soochow UniversityInstitute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical UniversityAbstract The high comorbidity of major depressive disorder (MDD) with other diseases has been well-documented. However, the pairwise causal connections for MDD comorbid networks are poorly characterized. We performed Phenome-wide Mendelian randomization (MR) analyses to explore bidirectional causal associations between MDD (N = 807,553) and 877 common diseases from FinnGen datasets (N = 377,277). The inverse variance weighting method was the primary technique, and other methods (weighted median and MR-Egger) were used for sensitivity analyses. Our MR analyses showed that the genetic liability to MDD is causally associated with the risks of 324 disease phenotypes (average b: 0.339), including 46 psychiatric and behavioral disorders (average b: 0.618), 18 neurological diseases (average b: 0.348), 44 respiratory diseases (average b: 0.345), 40 digestive diseases (average b: 0.281), 18 circulatory diseases (average b: 0.237), 37 genitourinary diseases (average b: 0.271), 66 musculoskeletal and connective diseases (average b: 0.326), 22 endocrine diseases (average b: 0.302), and others. In a reverse analysis, a total of 51 genetic components predisposing to various diseases were causally associated with MDD risk (average b: 0.086), including 5 infectious diseases (average b: 0.056), 11 neurological diseases (average b: 0.106), 14 oncological diseases (average b: 0.108), and 5 psychiatric and behavioral disorders (average b: 0.114). Bidirectional causal associations were identified between MDD and 15 diseases. For most MR analyses, little evidence of heterogeneity and pleiotropy was detected. Our findings confirmed the extensive and significant causal role of genetic predisposition to MDD in contributing to human disease phenotypes, which were more pronounced than those seen in the reverse analysis of the causal influences of other diseases on MDD.https://doi.org/10.1038/s41398-024-03216-z |
| spellingShingle | Wenxi Sun Ancha Baranova Dongming Liu Hongbao Cao Xiaobin Zhang Fuquan Zhang Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases Translational Psychiatry |
| title | Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases |
| title_full | Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases |
| title_fullStr | Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases |
| title_full_unstemmed | Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases |
| title_short | Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases |
| title_sort | phenome wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases |
| url | https://doi.org/10.1038/s41398-024-03216-z |
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