Abstract
ObjectivesPeriodontitis (PD) has been linked to arthritis in previous epidemiological observational studies; however, the results are inconclusive. It remains unclear whether the association between PD and arthritis is causal. The purpose of this study was to investigate the causal association of PD with arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA).MethodsWe performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy.ResultsGenetically determined PD did not have a causal effect on OA (OR = 1.06, 95% CI: 0.99-1.15, P = 0.09) and RA (OR = 0.99, 95% CI: 0.87-1.13, P = 0.89). Furthermore, we did not find a significant causal effect of arthritis on PD in the reverse MR analysis. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates according to the sensitivity analysis.ConclusionsOur MR analysis reveals non-causal association of PD with arthritis, despite observational studies reporting an association between PD and arthritis.
Highlights
Arthritis is an acute or chronic inflammation of the joints that is typically accompanied by pain and structural damage [1]
One PD-associated SNP of the five unavailable SNPs was replaced by proxy SNP rs4969455 with R2 > 0.8, and none of the genetic variants was palindromic with intermediate allele frequencies
Detailed information of IVs for PD and subtypes was listed in Supplementary Table 1
Summary
Arthritis is an acute or chronic inflammation of the joints that is typically accompanied by pain and structural damage [1]. Periodontitis, Mendelian Randomization characterized by inflammation of the synovial membrane which imposes a tremendous burden on the individual and society [3]. OA is a whole-joint disease characterized by articular cartilage loss and alterations in the subchondral bone [5]. Emerging evidence suggested that systemic inflammation may play a role in the development of OA and synovium inflammation is implicated in the pathogenesis of OA [6]. OA is becoming more prevalent with the combined effects of ageing and increasing obesity, and approximately 250 million individuals worldwide are currently affected by this disease [7]
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