Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis
Abstract Background Psoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints or both. However, deeper insight into the genetic susceptibility of psoriasis is still unclear. Methods Here we performed the largest multi-ancestry meta-analysis of genome-wide assoc...
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2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-06015-8 |
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| author | Min Zhang Wenting Su Jiahui Deng Bin Zhai Gaizhi Zhu Ran Gao Qi Zeng Jinming Qiu Ziqing Bian He Xiao Guoming Luan Renxi Wang |
| author_facet | Min Zhang Wenting Su Jiahui Deng Bin Zhai Gaizhi Zhu Ran Gao Qi Zeng Jinming Qiu Ziqing Bian He Xiao Guoming Luan Renxi Wang |
| author_sort | Min Zhang |
| collection | DOAJ |
| description | Abstract Background Psoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints or both. However, deeper insight into the genetic susceptibility of psoriasis is still unclear. Methods Here we performed the largest multi-ancestry meta-analysis of genome-wide association study including 28,869 psoriasis cases and 443,950 healthy controls. Results We identified 74 genome-wide significant loci for psoriasis. Of 74 loci, 32 were novel psoriasis risk loci. Across 74 loci, 801 likely causal genes are indicated and 164 causal genes are prioritized. SNP-based heritability analyses demonstrated that common variants explain 15% of genetic risk for psoriasis. Gene-set analyses and the genetic correlation revealed that psoriasis-related genes have the positive correlations with autoimmune diseases such as ulcerative colitis, inflammatory bowel diseases, and Crohn’s disease. Gene-drug interaction analysis suggested that psoriasis-associated genes overlapped with targets of current medications for psoriasis. Finally, we used the multi-ancestry meta-analysis to explore drug repurposing and the potential targets for psoriasis. Conclusions We identified 74 genome-wide significant loci for psoriasis. Based on 74 loci, we provided new biological insights to the etiology of psoriasis. Of clinical interest, we gave some hints for 76 potential targets and drug repurposing for psoriasis. |
| format | Article |
| id | doaj-art-d30340b19d8e48ba964b719f38e00ac2 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-d30340b19d8e48ba964b719f38e00ac22025-02-02T12:40:24ZengBMCJournal of Translational Medicine1479-58762025-01-0123111910.1186/s12967-024-06015-8Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasisMin Zhang0Wenting Su1Jiahui Deng2Bin Zhai3Gaizhi Zhu4Ran Gao5Qi Zeng6Jinming Qiu7Ziqing Bian8He Xiao9Guoming Luan10Renxi Wang11Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical UniversityBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical UniversityDepartment of Neurosurgery, SanBo Brain Hospital, Capital Medical UniversityDepartment of Hematology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General HospitalBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical UniversityBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical UniversityBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical UniversityBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical UniversityBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical UniversityState Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and ToxicologyDepartment of Neurosurgery, SanBo Brain Hospital, Capital Medical UniversityBeijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical UniversityAbstract Background Psoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints or both. However, deeper insight into the genetic susceptibility of psoriasis is still unclear. Methods Here we performed the largest multi-ancestry meta-analysis of genome-wide association study including 28,869 psoriasis cases and 443,950 healthy controls. Results We identified 74 genome-wide significant loci for psoriasis. Of 74 loci, 32 were novel psoriasis risk loci. Across 74 loci, 801 likely causal genes are indicated and 164 causal genes are prioritized. SNP-based heritability analyses demonstrated that common variants explain 15% of genetic risk for psoriasis. Gene-set analyses and the genetic correlation revealed that psoriasis-related genes have the positive correlations with autoimmune diseases such as ulcerative colitis, inflammatory bowel diseases, and Crohn’s disease. Gene-drug interaction analysis suggested that psoriasis-associated genes overlapped with targets of current medications for psoriasis. Finally, we used the multi-ancestry meta-analysis to explore drug repurposing and the potential targets for psoriasis. Conclusions We identified 74 genome-wide significant loci for psoriasis. Based on 74 loci, we provided new biological insights to the etiology of psoriasis. Of clinical interest, we gave some hints for 76 potential targets and drug repurposing for psoriasis.https://doi.org/10.1186/s12967-024-06015-8PsoriasisMeta-analysisGenetic variantsGWASRisk loci |
| spellingShingle | Min Zhang Wenting Su Jiahui Deng Bin Zhai Gaizhi Zhu Ran Gao Qi Zeng Jinming Qiu Ziqing Bian He Xiao Guoming Luan Renxi Wang Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis Journal of Translational Medicine Psoriasis Meta-analysis Genetic variants GWAS Risk loci |
| title | Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis |
| title_full | Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis |
| title_fullStr | Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis |
| title_full_unstemmed | Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis |
| title_short | Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis |
| title_sort | multi ancestry genome wide meta analysis with 472 819 individuals identifies 32 novel risk loci for psoriasis |
| topic | Psoriasis Meta-analysis Genetic variants GWAS Risk loci |
| url | https://doi.org/10.1186/s12967-024-06015-8 |
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