Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder
BACKGROUND Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are highly comorbid and exhibit strong correlations with one another. We aimed to investigate mechanisms of underlying relationships between PTSD and 3 kinds of depressive phenotypes, namely, MDD, depressed affect (D...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2022-02-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI145942 |
| _version_ | 1818549439374032896 |
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| author | Fuquan Zhang Shuquan Rao Hongbao Cao Xiangrong Zhang Qiang Wang Yong Xu Jing Sun Chun Wang Jiu Chen Xijia Xu Ning Zhang Lin Tian Jianmin Yuan Guoqiang Wang Lei Cai Mingqing Xu Ancha Baranova |
| author_facet | Fuquan Zhang Shuquan Rao Hongbao Cao Xiangrong Zhang Qiang Wang Yong Xu Jing Sun Chun Wang Jiu Chen Xijia Xu Ning Zhang Lin Tian Jianmin Yuan Guoqiang Wang Lei Cai Mingqing Xu Ancha Baranova |
| author_sort | Fuquan Zhang |
| collection | DOAJ |
| description | BACKGROUND Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are highly comorbid and exhibit strong correlations with one another. We aimed to investigate mechanisms of underlying relationships between PTSD and 3 kinds of depressive phenotypes, namely, MDD, depressed affect (DAF), and depression (DEP, including both MDD and the broad definition of depression).METHODS Genetic correlations between PTSD and the depressive phenotypes were tested using linkage disequilibrium score regression. Polygenic overlap analysis was used to estimate shared and trait-specific causal variants across a pair of traits. Causal relationships between PTSD and the depressive phenotypes were investigated using Mendelian randomization. Shared genomic loci between PTSD and MDD were identified using cross-trait meta-analysis.RESULTS Genetic correlations of PTSD with the depressive phenotypes were in the range of 0.71–0.80. The estimated numbers of causal variants were 14,565, 12,965, 10,565, and 4,986 for MDD, DEP, DAF, and PTSD, respectively. In each case, causal variants contributing to PTSD were completely or largely covered by causal variants defining each of the depressive phenotypes. Mendelian randomization analysis indicated that the genetically determined depressive phenotypes confer a causal effect on PTSD (b = 0.21–0.31). Notably, genetically determined PTSD confers a causal effect on DEP (b = 0.14) and DAF (b = 0.15), but not MDD. Cross-trait meta-analysis of MDD and PTSD identified 47 genomic loci, including 29 loci shared between PTSD and MDD.CONCLUSION Evidence from shared genetics suggests that PTSD is a subtype of MDD. This study provides support to the efforts in reducing diagnostic heterogeneity in psychiatric nosology.FUNDING The National Key Research and Development Program of China and the National Natural Science Foundation of China. |
| first_indexed | 2024-12-12T08:33:21Z |
| format | Article |
| id | doaj.art-78190ba994d14b5fbf2ccd5337449452 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-12-12T08:33:21Z |
| publishDate | 2022-02-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-78190ba994d14b5fbf2ccd53374494522022-12-22T00:31:02ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-02-011323Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorderFuquan ZhangShuquan RaoHongbao CaoXiangrong ZhangQiang WangYong XuJing SunChun WangJiu ChenXijia XuNing ZhangLin TianJianmin YuanGuoqiang WangLei CaiMingqing XuAncha BaranovaBACKGROUND Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are highly comorbid and exhibit strong correlations with one another. We aimed to investigate mechanisms of underlying relationships between PTSD and 3 kinds of depressive phenotypes, namely, MDD, depressed affect (DAF), and depression (DEP, including both MDD and the broad definition of depression).METHODS Genetic correlations between PTSD and the depressive phenotypes were tested using linkage disequilibrium score regression. Polygenic overlap analysis was used to estimate shared and trait-specific causal variants across a pair of traits. Causal relationships between PTSD and the depressive phenotypes were investigated using Mendelian randomization. Shared genomic loci between PTSD and MDD were identified using cross-trait meta-analysis.RESULTS Genetic correlations of PTSD with the depressive phenotypes were in the range of 0.71–0.80. The estimated numbers of causal variants were 14,565, 12,965, 10,565, and 4,986 for MDD, DEP, DAF, and PTSD, respectively. In each case, causal variants contributing to PTSD were completely or largely covered by causal variants defining each of the depressive phenotypes. Mendelian randomization analysis indicated that the genetically determined depressive phenotypes confer a causal effect on PTSD (b = 0.21–0.31). Notably, genetically determined PTSD confers a causal effect on DEP (b = 0.14) and DAF (b = 0.15), but not MDD. Cross-trait meta-analysis of MDD and PTSD identified 47 genomic loci, including 29 loci shared between PTSD and MDD.CONCLUSION Evidence from shared genetics suggests that PTSD is a subtype of MDD. This study provides support to the efforts in reducing diagnostic heterogeneity in psychiatric nosology.FUNDING The National Key Research and Development Program of China and the National Natural Science Foundation of China.https://doi.org/10.1172/JCI145942Genetics |
| spellingShingle | Fuquan Zhang Shuquan Rao Hongbao Cao Xiangrong Zhang Qiang Wang Yong Xu Jing Sun Chun Wang Jiu Chen Xijia Xu Ning Zhang Lin Tian Jianmin Yuan Guoqiang Wang Lei Cai Mingqing Xu Ancha Baranova Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder The Journal of Clinical Investigation Genetics |
| title | Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder |
| title_full | Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder |
| title_fullStr | Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder |
| title_full_unstemmed | Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder |
| title_short | Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder |
| title_sort | genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder |
| topic | Genetics |
| url | https://doi.org/10.1172/JCI145942 |
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