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Abstract

7. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31: 315– 24. 8. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014;506:376– 81. 9. Zillikens MC, Demissie S, Hsu YH, YergesArmstrong LM, Chou WC, Stolk L, et al. Large metaanalysis of genomewide association studies identifies five loci for lean body mass. Nat Commun 2017;8:80. each exposure. Each standard deviation increase in wholebody fat mass and body fat percentage was causally associated with a higher likelihood of RA (for wholebody fat mass, odds ratio [OR] 1.41 [95% confidence interval (95% CI) 1.09– 1.84]; for body fat percentage, OR 1.68 [95% CI 1.31– 2.16]) (Figure 1). In contrast, wholebody fatfree mass and appendicular lean mass were not associated with an increased risk of RA. There was no significant indication of horizontal pleiotropy in sensitivity analyses. Using genetically predicted body fat measures, we showed a significant causal relationship between fat mass and RA risk, but not between fat-free mass and RA. These results are more robust than those from traditional observational methods, which may be influenced by reverse causation. Proinflammatory states created by excess adiposity increase RA risk and represent a target for intervention in those deemed at high risk. The main strength of this study is the range of body composition measures assessed in a large population. However, data were limited to a population of European ancestry, and findings may not be directly extrapolated to other populations. Bioelectrical impedance strongly correlated (r = 0.83) with the gold standard of dual x-ray absorptiometry, and showed no evidence of heterogeneity when results of both methods were meta-analyzed (9). In summary, fat mass has a causal relationship with RA risk but not fatfree mass.