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. 2023 Oct 9:14:1251167.
doi: 10.3389/fendo.2023.1251167. eCollection 2023.

Inflammatory arthritis and eye diseases: a Mendelian randomization study

Xinlin Nie  1 , Zhaoliang Liu  1 , Dongheng Xie  1 , Yang Sun  1
Affiliations

Inflammatory arthritis and eye diseases: a Mendelian randomization study

Xinlin Nie et al. Front Endocrinol (Lausanne). .

Abstract

Objectives: The aim of this study was to determine causal associations between inflammatory arthritis and eye diseases (disorders of sclera, cornea, iris, and ciliary body [DSCIC] and disorders of choroid and retina [DCR]).

Methods: Genome-wide association studies' summary data of rheumatoid arthritis (RA) from a large-scale meta-analysis were used to identify genetically predicted RA. UK Biobank source data predicted ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA). Furthermore, data from the FinnGen Biobank were used to identify genetically predicted eye diseases. Two-sample Mendelian randomization analysis was used to assess the causal relationship between inflammatory arthritis and eye diseases in the European population. Inverse-variance weighting (IVW) was used as the primary method, while MR-Egger, weighted median, and MR-PRESSO outlier test were used to detect heterogeneity and pleiotropy.

Results: Genetically determined RA was indeed observed to have a causal effect on DSCIC (odds ratio [OR] = 1.084, p = 2.353 × 10-10) and DCR (OR = 1.151, p = 1.584 × 10-19). AS was causally associated with DSCIC (OR = 1.068, p < 2.024 × 10-8). In addition, PsA was also found to have a causal association with an increased risk of 17.9% for the development of DSCIC (OR = 1.179, p = 0.003). On the flip side, DSCIC increased the risk of JIA (OR = 2.276, p = 0.003).

Conclusion: Our study provided genetic evidence for the causal associations of RA, AS, and PsA with an increased risk of DSCIC, and a causal association between RA and DCR was also identified. In addition, DSCIC greatly increased the risk of JIA.

Keywords: Mendelian randomization; ankylosing spondylitis; eye diseases; inflammatory arthritis; psoriatic arthritis; rheumatoid arthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of a Mendelian randomization study. Green lines represent separate threshold (p < 5×10-6) for JIA screening of instrument variables. MR, Mendelian randomization; OR, odds ratio; CI, confidence interval; RA, rheumatoid arthritis; AS, ankylosing spondylitis; PsA, psoriatic arthritis; JIA, juvenile idiopathic arthritis; DSCIC, Disorders of sclera, cornea, iris, and ciliary body; DCR, Disorders of choroid and retina.
Figure 2
Figure 2
Schematic representation of Mendelian randomization analysis. Inflammatory arthritis and eye diseases as exposure and outcome, respectively, and the instrumental variables must meet three major assumptions. IVs, instrument variables; SNPs, single-nucleotide polymorphisms;①, Correlation assumption; ②, Exclusivity assumption; ③, Independence assumption.
Figure 3
Figure 3
Forest plot for MR analyses. OR, odds ratio; CI, confidence interval; IVW, Inverse-variance weighting; RA, rheumatoid arthritis; AS, ankylosing spondylitis; PsA, psoriatic arthritis; JIA, juvenile idiopathic arthritis; DSCIC, Disorders of sclera, cornea, iris and ciliary body; DCR, Disorders of choroid and retina.
See this image and copyright information in PMC

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