AUTHOR=Hong Jianqiao , Qu Zihao , Ji Xiaoxiao , Li Congsun , Zhang Geng , Jin Ciliang , Wang Jie , Zhang Yongxing , Shen Yue , Meng Jiahong , Zhou Chenhe , Fang Chaohua , Wang Wei , Yan Shigui 

TITLE=Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.707617

DOI=10.3389/fimmu.2021.707617

ISSN=1664-3224

ABSTRACT=Objectives
To find out the genetic association between IL6 and autoimmune arthritis.
Methods
We performed a two‐sample Mendelian randomization (MR) study, using multiple genome-wide association studies (GWAS) datasets. Further, a sex-stratified MR study was performed to identified 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.
Results 
The MR result denoted a genetic association between 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 negatively correlation with 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 male population, with RA in female population and with PsA in male population. Additionally, ADAR, a gene identified by the sensitive test, could be the reason for non-significant association between IL6 and PsA in pooled population.
Conclusion
Our findings showed that overactive IL6 signal pathway led to autoimmune arthritis, especially in RA and AS. The Sexual differences was also observed in IL6-intermediate susceptibility to autoimmune arthritis.