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

• Lee YH
• Song GG

• KMID: 2514120
• DOI: http://doi.org/10.4078/jrd.2021.28.2.94

Abstract

Objective
The aim of this study was to examine if the intestinal microbiome is causally correlated with osteoarthritis (OA) incidence.
Methods
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.
Results
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.
Conclusion
The findings of the MR analysis did not support a causal relationship between intestinal microbiome and OA risk.

Keyword

Gut microbiome; Osteoarthritis; Mendelian randomization analysis

Figure

• 

  Figure 1 Manhattan plots for IV SNPs from gut microbiome GWAS. The dark horizontal line indicates genome-wide signifi-cance. SNP: single nucleotide polymorphism, GWAS: genome- wide association study, IV: instrumental variable.

• 

  Figure 2 Forest plot of the causal effects of gut microbiome-associated single-nucleotide polymorphisms on osteoarthritis. IVW: inverse variance weighting, MR: Mendelian randomization.

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  Figure 3 Scatter plots of genetic associations with gut microbiome against the genetic associations with osteoarthritis. The slopes of each line represent the causal association for each method. The dash line represents the inverse-variance weighting estimate; the dot line, the weighted median estimate; and the linear line, the Mendelian randomization‐Egger estimate. SNP: single nucleotide polymorphism.

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  Figure 4 “Leave-one-out” analysis to investigate the possibility of the causal association being driven by a unique single-nucleotide polymorphism. MR: Mendelian randomization.

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