Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific
ObjectivesTo find out the genetic association between IL6 and autoimmune arthritis.MethodsWe performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.707617/full |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jianqiao Hong Jianqiao Hong Jianqiao Hong Zihao Qu Zihao Qu Zihao Qu Xiaoxiao Ji Xiaoxiao Ji Xiaoxiao Ji Congsun Li Congsun Li Congsun Li Geng Zhang Geng Zhang Geng Zhang Ciliang Jin Jie Wang Jie Wang Jie Wang Yongxing Zhang Yongxing Zhang Yongxing Zhang Yue Shen Yue Shen Yue Shen Jiahong Meng Jiahong Meng Jiahong Meng Chenhe Zhou Chenhe Zhou Chenhe Zhou Chaohua Fang Wei Wang Wei Wang Wei Wang Shigui Yan Shigui Yan Shigui Yan |
| spellingShingle |
Jianqiao Hong Jianqiao Hong Jianqiao Hong Zihao Qu Zihao Qu Zihao Qu Xiaoxiao Ji Xiaoxiao Ji Xiaoxiao Ji Congsun Li Congsun Li Congsun Li Geng Zhang Geng Zhang Geng Zhang Ciliang Jin Jie Wang Jie Wang Jie Wang Yongxing Zhang Yongxing Zhang Yongxing Zhang Yue Shen Yue Shen Yue Shen Jiahong Meng Jiahong Meng Jiahong Meng Chenhe Zhou Chenhe Zhou Chenhe Zhou Chaohua Fang Wei Wang Wei Wang Wei Wang Shigui Yan Shigui Yan Shigui Yan Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific Frontiers in Immunology Mendelian randomization IL6 sIL6R autoimmune arthritis ADAR |
| author_facet |
Jianqiao Hong Jianqiao Hong Jianqiao Hong Zihao Qu Zihao Qu Zihao Qu Xiaoxiao Ji Xiaoxiao Ji Xiaoxiao Ji Congsun Li Congsun Li Congsun Li Geng Zhang Geng Zhang Geng Zhang Ciliang Jin Jie Wang Jie Wang Jie Wang Yongxing Zhang Yongxing Zhang Yongxing Zhang Yue Shen Yue Shen Yue Shen Jiahong Meng Jiahong Meng Jiahong Meng Chenhe Zhou Chenhe Zhou Chenhe Zhou Chaohua Fang Wei Wang Wei Wang Wei Wang Shigui Yan Shigui Yan Shigui Yan |
| author_sort |
Jianqiao Hong |
| title |
Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific |
| title_short |
Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific |
| title_full |
Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific |
| title_fullStr |
Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific |
| title_full_unstemmed |
Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific |
| title_sort |
genetic associations between il-6 and the development of autoimmune arthritis are gender-specific |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2021-09-01 |
| description |
ObjectivesTo find out the genetic association between IL6 and autoimmune arthritis.MethodsWe performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in the association between IL6 and autoimmune arthritis. Then, LocusZoom plots were displayed based on the IL6R gene region to present evidence of genetic colocalization between diseases.ResultsThe MR result denoted a genetic association between the increased level of IL-6 signaling and risk of RA (β=0.325, 95%CI 0.088, 0.561, p=7.08E-03) and AS (β=1.240, 95%CI 0.495, 1.980, p=1.1E-03). Accordingly, sIL6R was found to have negatively correlation with the onset of RA (β=-0.020, 95%CI -0.0320, -0.008, p=1.18E-03) and AS (β=-0.125, 95%CI -0.177, -0.073, p=2.29E-06). However, no genetic association between IL6/sIL6R and PsA was detected. The gender-stratified MR analysis showed that IL6 was associated with AS in the male population, with RA in the female population, and with PsA in the male population. Additionally, ADAR, a gene identified by a sensitive test, could be the reason for the nonsignificant association between IL6 and PsA in a pooled population.ConclusionOur findings showed that the overactive IL6 signal pathway led to autoimmune arthritis, especially in RA and AS. Sexual difference was also observed in IL6-intermediate susceptibility to autoimmune arthritis. |
| topic |
Mendelian randomization IL6 sIL6R autoimmune arthritis ADAR |
| url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.707617/full |
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doaj-a4334bb094504cbbb00e678d7dbb25c82021-09-04T11:28:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.707617707617Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-SpecificJianqiao Hong0Jianqiao Hong1Jianqiao Hong2Zihao Qu3Zihao Qu4Zihao Qu5Xiaoxiao Ji6Xiaoxiao Ji7Xiaoxiao Ji8Congsun Li9Congsun Li10Congsun Li11Geng Zhang12Geng Zhang13Geng Zhang14Ciliang Jin15Jie Wang16Jie Wang17Jie Wang18Yongxing Zhang19Yongxing Zhang20Yongxing Zhang21Yue Shen22Yue Shen23Yue Shen24Jiahong Meng25Jiahong Meng26Jiahong Meng27Chenhe Zhou28Chenhe Zhou29Chenhe Zhou30Chaohua Fang31Wei Wang32Wei Wang33Wei Wang34Shigui Yan35Shigui Yan36Shigui Yan37Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaJoint Surgery, Ningbo 6th Hospital, Ningbo, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaOrthopedic Research Institute of Zhejiang University, Hangzhou, ChinaKey Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, ChinaObjectivesTo find out the genetic association between IL6 and autoimmune arthritis.MethodsWe performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in the association between IL6 and autoimmune arthritis. Then, LocusZoom plots were displayed based on the IL6R gene region to present evidence of genetic colocalization between diseases.ResultsThe MR result denoted a genetic association between the increased level of IL-6 signaling and risk of RA (β=0.325, 95%CI 0.088, 0.561, p=7.08E-03) and AS (β=1.240, 95%CI 0.495, 1.980, p=1.1E-03). Accordingly, sIL6R was found to have negatively correlation with the onset of RA (β=-0.020, 95%CI -0.0320, -0.008, p=1.18E-03) and AS (β=-0.125, 95%CI -0.177, -0.073, p=2.29E-06). However, no genetic association between IL6/sIL6R and PsA was detected. The gender-stratified MR analysis showed that IL6 was associated with AS in the male population, with RA in the female population, and with PsA in the male population. Additionally, ADAR, a gene identified by a sensitive test, could be the reason for the nonsignificant association between IL6 and PsA in a pooled population.ConclusionOur findings showed that the overactive IL6 signal pathway led to autoimmune arthritis, especially in RA and AS. Sexual difference was also observed in IL6-intermediate susceptibility to autoimmune arthritis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.707617/fullMendelian randomizationIL6sIL6Rautoimmune arthritisADAR |