J Rheum Dis.  2021 Apr;28(2):94-100. 10.4078/jrd.2021.28.2.94.

The Gut Microbiome and Osteoarthritis: A Two-Sample Mendelian Randomization Study

  • 1Department of Rheumatology, Korea University College of Medicine, Seoul, Korea


The aim of this study was to examine if the intestinal microbiome is causally correlated with osteoarthritis (OA) incidence.
A two-sample Mendelian randomization (MR) study was conducted using inverse variance weighting (IVW), weighted median, and MR-Egger regression techniques. Publicly accessible summary statistics dataset of intestinal microbiomes of European descent from genome-wide association studies (GWASs) (a total with 3,326 individuals) was used as an exposure. As an outcome, summary data from the GWAS include 3,498 patients with OA of the knee and hip from the arcOGEN sample and 11,009 controls of European descent.
We identified 29 single-nucleotide polymorphisms from GWAS of intestinal microbiomes as instrumental variables. The IVW approach found no evidence to suggest a causal relationship between the intestinal microbiota and OA (beta=−0.001, standard error [SE]=0.004, p=0.748). The regression test of MR-Egger showed that the directional pleiotropy was unlikely to be a bias (intercept=0.002, SE=0.007, p=0.697) and the MR-Egger study showed no causal relation between the intestinal microbiota and the OA (beta=−0.002, SE=0.005, p=0.630). The weighted median analysis also did not have indications of a causal relationship between the intestinal microbiota and OA (beta=−0.002, SE=0.005, p=0.630). The MR results calculated using IVW, the median weighted and the MR-Egger regression approaches were consistent.
The findings of the MR analysis did not support a causal relationship between intestinal microbiome and OA risk.


Gut microbiome; Osteoarthritis; Mendelian randomization analysis
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