RT Journal Article
SR Electronic
T1 Genome-Wide Mapping of Plasma IgG N-Glycan Quantitative Trait Loci Identifies a Potentially Causal Association between IgG N-Glycans and Rheumatoid Arthritis
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 2508
OP 2514
DO 10.4049/jimmunol.2100080
VO 208
IS 11
A1 Liu, Di
A1 Dong, Jing
A1 Zhang, Jie
A1 Xu, Xizhu
A1 Tian, Qiuyue
A1 Meng, Xiaoni
A1 Wu, Lijuan
A1 Zheng, Deqiang
A1 Chu, Xi
A1 Wang, Wei
A1 Meng, Qun
A1 Wang, Youxin
YR 2022
UL http://www.jimmunol.org/content/208/11/2508.abstract
AB We identified potentially causal associations of IgG N-glycans with RA.Our findings shed light on IgG N-glycosylation involvement in RA.Observational studies highlight associations of IgG N-glycosylation with rheumatoid arthritis (RA); however, the causality between these conditions remains to be determined. Standard and multivariable two-sample Mendelian randomization (MR) analyses integrating a summary genome-wide association study for RA and IgG N-glycan quantitative trait loci (IgG N-glycan-QTL) data were performed to explore the potentially causal associations of IgG N-glycosylation with RA. After correcting for multiple testing (p < 2 × 10−3), the standard MR analysis based on the inverse-variance weighted method showed a significant association of genetically instrumented IgG N-glycan (GP4) with RA (odds ratioGP4 = 0.906, 95% confidence interval = 0.857–0.958, p = 5.246 × 10−4). In addition, we identified seven significant associations of genetically instrumented IgG N-glycans with RA by multivariable MR analysis (p < 2 × 10−3). Results were broadly consistent in sensitivity analyses using MR_Lasso, MR_weighted median, MR_Egger regression, and leave-one-out analysis with different instruments (all p values <0.05). There was limited evidence of pleiotropy bias (all p values > 0.05). In conclusion, our MR analysis incorporating genome-wide association studies and IgG N-glycan-QTL data revealed that IgG N-glycans were potentially causally associated with RA. Our findings shed light on the role of IgG N-glycosylation in the development of RA. Future studies are needed to validate our findings and to explore the underlying physiological mechanisms in the etiology of RA.