Causal relationship between five autoimmune diseases and intervertebral disc degeneration:a bidirectional Mendelian analysis.
10.12200/j.issn.1003-0034.20240413
- Author:
Bao-Fei ZHANG
1
;
Xun-Lu YIN
2
;
Ze-Ling HUANG
3
;
Shuai PEI
3
;
Yu-Wei LI
2
,
4
,
5
Author Information
1. Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215008, Jiangsu, China; Qufu Hospital of Traditional Chinese Medicine, Qufu 273100, Shandong, China.
2. Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China.
3. Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215008, Jiangsu, China.
4. Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215008, Jiangsu, China;
5. Qufu Hospital of Traditional Chinese Medicine, Qufu 273100, Shandong, China;
- Publication Type:Journal Article
- Keywords:
Autoimmune disease;
Causal inference;
Disc degeneration;
Immune privilege;
Mendelian randomization
- MeSH:
Humans;
Intervertebral Disc Degeneration/etiology*;
Mendelian Randomization Analysis;
Autoimmune Diseases/complications*;
Genome-Wide Association Study;
Spondylitis, Ankylosing/genetics*;
Arthritis, Rheumatoid/genetics*
- From:
China Journal of Orthopaedics and Traumatology
2025;38(8):856-866
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the potential causal relationship between intervertebral disc degeneration and certain autoimmune diseases.
METHODS:Genome-wide association study (GWAS) data of 5 autoimmune diseases were obtained from large-scale GWAS databases. Data on internal vertebral disc degeneration (IVDD) were derived from the FinnGen consortium, which included 294, 770 controls and 41, 669 cases. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to investigate the potential causal relationship between the 5 autoimmune diseases and IVDD. Multiple analytical methods were adopted, including MR methods such as inverse variance weighting(IVW), MR-Egger, weighted median, weighted mode, and simple mode. Cochran's Q test, leave-one-out analysis, and MR-Egger intercept test were conducted to assess heterogeneity, robustness, and pleiotropy. For the robustness of the results, MR-PRESSO was used to detect outliers, and MR analysis was re-conducted after removing the outliers.
RESULTS:The MR analysis results showed that there might be a bidirectional causal relationship between ankylosing spondylitis(AS) and IVDD:AS on IVDD, OR=1.038, 95%CI (1.024, 1.053), P=0.000;and IVDD on AS, OR=2.117, 95%CI(1.065, 4.207), P=0.032. There might be a positive correlation between IVDD and rheumatoid arthritis(RA) as well as systemic lupus erythematosus(SLE):IVDD on RA, OR=1.184, 95%CI(1.071, 1.309), P=0.001;and IVDD on SLE, OR=1.678, 95%CI(1.187, 2.372), P=0.003. There was no significant correlation between ulcerative colitis(UC), autoimmune thyroiditis(ATD) and IVDD. After removing outliers by MR-PRESSO and re-conducting MR analysis, the results did not change qualitatively. Sensitivity analysis indicated that the results were robust to potential sources of bias.
CONCLUSION:AS and IVDD may be risk factors for each other, and IVDD may be a potential risk factor for RA and SLE. These findings provide a basis for guiding the prevention and combined diagnosis and treatment of IVDD, AS, RA, and SLE, while the specific underlying mechanisms still require further experimental basic research.
