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Non-causal association of gut microbiome on the risk of rheumatoid arthritis: a Mendelian randomisation study
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  1. Jun Inamo
  1. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
  1. Correspondence to Dr Jun Inamo, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; inamoj{at}gmail.com

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I read with great interest the article by Alpizar-Rodriguez et al regarding the risk of intestinal dysbiosis, particularly Prevotella spp enrichment, in preclinical rheumatoid arthritis (RA).1 Immune response in gut is assumed to be one of the triggers of development of RA.2 However, it is hard to assess causal association by case–control study due to limitations such as latent confounding factors; dysbiosis first or RA first. Therefore, to investigate causal effect of gut microbiome on the development of RA, I conducted Mendelian randomisation (MR) analysis.3 MR is useful to investigate causal association among phenotypes and/or biomarkers because it is based on genetic variation to mimic the design of randomised controlled trials. In MR, single nucleotide polymorphisms (SNP) are expected to be random and causally upstream of the exposure; thus, SNP are used as instrumental variables (IVs) in MR.

I used the publicly available two data sets of genome-wide association studies (GWASs) for gut microbiome (totally 3326 individuals) of European ancestry as the exposure4 5 and one data …

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