J Rheum Dis.  2020 Apr;27(2):88-95. 10.4078/jrd.2020.27.2.88.

The Uric Acid and Gout have No Direct Causality With Osteoarthritis: A Mendelian Randomization Study

• Lee YH
• Song GG

• KMID: 2471949
• DOI: http://doi.org/10.4078/jrd.2020.27.2.88

Abstract

OBJECTIVE
To examine whether uric acid level or gout is causally associated with the risk of osteoarthritis.
METHODS
We performed a two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods. We used the publicly available summary statistics datasets of uric acid level or gout genome-wide association studies (GWASs) as the exposure, and a GWAS in 3,498 patients with osteoarthritis in the arcOGEN study and 11,009 controls of European ancestry as the outcome.
RESULTS
Six single nucleotide polymorphisms (SNPs) from the GWAS data on uric acid level and 12 SNPs from the GWAS data on gout were selected as instrumental variables (IVs). The IVW analysis did not support a causal association between uric acid level or gout and risk of osteoarthritis (beta=−0.026, standard error [SE]=0.096, p=0.789; beta=−0.018, SE=0.025, p=0.482). MR-Egger regression revealed no causal association between uric acid level or gout and risk of osteoarthritis (beta=0.028, SE=0.142, p=0.852; beta=−0.056, SE=0.090, p=0.548). Similarly, no evidence of a casual association was provided by the weighted median approach (beta=0.004, SE=0.064, p=0.946; beta=−0.005, SE=0.025, p=0.843).
CONCLUSION
The results of MR analysis demonstrates that uric acid level and gout may be not causally associated with the increased risk of osteoarthritis. Considering MR study is not susceptible to bias from unmeasured confounders or reverse causation, the epidemiological evidence for an association between uric acid level or gout and a higher risk of osteoarthritis may be due to residual confounding or reverse causation rather than direct causality.

Keyword

Uric acid; Gout; Osteoarthritis; Mendelian randomization analysis

MeSH Terms

Bias (Epidemiology)
Dataset
Genome-Wide Association Study
Gout*
Humans
Mendelian Randomization Analysis
Osteoarthritis*
Polymorphism, Single Nucleotide
Random Allocation*
Uric Acid*
Uric Acid

Figure

• 

  Figure 1. Forrest plot of the causal effects of uric acid level (A) or gout (B)-associated SNPs on osteoarthritis. SNP: single nucleotide polymorphism, MR: Mendelian randomization, IVW: inverse-variance weighted, Na: not available.

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  Figure 2. Scatter plots of genetic associations of uric acid level (A) or gout (B) against the genetic associations of osteoarthritis. The slopes of each line represent the causal association for each method. Blue line represents the IVW estimate, green line represents the weighted median estimate, and dark blue line represents the MR-Egger estimate. IVW: inverse-variance weighted, SNP: single nucleotide polymorphism, MR: Mendelian randomization, Na: not available.

• 

  Figure 3. Funnel plot to assess the heterogeneity of the causal effects of uric acid level (A) or gout (B)-associated SNPs on osteoarthritis. Blue line represents the IVW estimate, and dark blue line represents the MR-Egger estimate. SNP: single nucleotide polymorphism, IVW: inverse-variance weighted, MR: Mendelian randomization, SE: standard error, β: beta coefficient.

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