Causal relationship between rheumatoid arthritis and ankylosing spondylitis: Two-sample Mendelian randomization.

To investigate the causal relationship between rheumatoid arthritis (RA) and ankylosing spondylitis using Mendelian randomization (MR). Genetic loci independently associated with RA and ankylosing spondylitis in people of European origin were selected as instrumental variables using pooled data from large-scale genome-wide association studies. Three MR analyses, MR-Egger, weighted median, and inverse variance weighting, were used to investigate the causal relationship between RA and ankylosing spondylitis. Heterogeneity and multiplicity tests were used, and a sensitivity test using the "leave-one-out" method was used to explore the robustness of the results. The inverse variance weighting results showed an OR (95 % CI) of 1.25 (1.11-1.41), P < .001, indicating a causal relationship between RA and ankylosing spondylitis. And no heterogeneity and pleiotropy were found by the test and sensitivity analysis also showed robust results. The present study was conducted to analyze and explore the genetic data using two-sample MR analysis and the results showed that there is a causal relationship between RA and the occurrence of ankylosing spondylitis.

Deng GH 《-》

Assessing the association of leukocyte telomere length with ankylosing spondylitis and rheumatoid arthritis: A bidirectional Mendelian randomization study.

Telomere length shortening can cause senescence and apoptosis in various immune cells, resulting in immune destabilization and ageing of the organism. In this study, we aimed to systematically assess the causal relationship of leukocyte telomere length (LTL) with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) using a Mendelian randomization study. LTL (n=472174) was obtained from the UK Biobank genome-wide association study pooled data. AS (n=229640), RA (n=212472) were obtained from FinnGen database. MR-Egger, inverse variance weighting, and weighted median methods were used to estimate the effects of causes. Cochran's Q test, MR Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots were used to look at sensitivity, heterogeneity, and multiple effects. Forward MR analysis considered LTL as the exposure and AS, RA as the outcome. Reverse MR analysis considered AS, RA as the exposure and LTL as the outcome. In the forward MR analysis, inverse variance-weighted and weighted median analysis results indicated that longer LTL might be associated with increased risk of AS (IVW: OR = 1.55, 95% CI: 1.14-2.11, p = 0.006). MR Egger regression analysis showed no pleiotropy between instrumental variables (IVs) (Egger intercept= 0.008, p = 0.294). The leave-one-out analysis showed that each single nucleotide polymorphism (SNP) of AS was robust to each outcome. No significant causal effects were found between AS, RA and LTL in the reverse MR analysis. Longer LTL may be related with an increased risk of developing AS, and these findings provide a foundation for future clinical research on the causal association between LTL and AS.

Wei D ，Jiang Y ，Cheng J ，Wang H ，Sha K ，Zhao J ... -  《Frontiers in Immunology》

Causality of occupational exposure on rheumatoid arthritis and ankylosing spondylitis: a two-sample mendelian randomization study.

Du K ，Zhang CY ，Li A ，Hu JZ ，Guo R ，Li SM ... -  《Frontiers in Immunology》

Potential association of rheumatic diseases with bone mineral density and fractures: a bi-directional mendelian randomization study.

Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516). RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.

Hong CX ，Pan YZ ，Dai FB 《BMC MUSCULOSKELETAL DISORDERS》

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases.

Chen C ，Yan S ，Wan B ，Yu Y ，Zeng J ，Tan L ，Lu J ... -  《-》