Child-to-adult body size trajectories and risk of rheumatoid arthritis: the mediating role of metabolic unhealthiness, low-grade inflammation, and the modifying effect of genetic susceptibility.

Authors

Xing-Yu Wan, Wei Huang, Yi-Xu Wang, Yi-Han Hu, Shi-Hao Jing, Chao Zhang, Rui-Xue Leng, Long Gu, Qi Wang, Dong-Sheng Di

Published in

Journal of autoimmunity. Volume 163. Pages 103612. Aug 06, 2026. Epub Aug 06, 2026.

Abstract

To investigate the association between body size changes from childhood to adulthood and rheumatoid arthritis (RA), considering the roles of metabolic unhealthiness, low-grade inflammation, and genetic susceptibility.
Data from the UK Biobank on 482,264 RA-free participants were divided into nine categories based on their self-reported body size at age 10 and measured BMI in adulthood. Cox regression models were used to estimate the associations of body size with RA. Mediation analysis quantified the indirect effects of metabolic and inflammatory factors. Interaction analyses examined the relationship between genetic predisposition and body size.
Both low and high body size at age 10 were associated with an increased risk of RA (HR = 1.07, 95% CI: 1.01-1.13 for low body size; HR = 1.16, 95% CI: 1.08-1.24 for high body size). In adulthood, low body size was associated with a reduced risk (HR = 0.84, 95% CI: 0.79-0.89), while high body size was associated with an increased risk (HR = 1.43, 95% CI: 1.35-1.53). Across life-course trajectories, risk was lower for paths ending in low adult body size with the lowest point estimate for Child_High-Adult_Low. By contrast, trajectories culminating in higher adult body size conferred increased risk, most notably Child_Low-Adult_High. Metabolic unhealthiness and low-grade inflammation partially mediated the associations between body size and RA risk. Significant interactive effects were detected between body size and genetic elements.
Our findings suggest that life-course weight management and metabolic health may be relevant to RA prevention, particularly among genetically susceptible individuals, though further translational studies are needed.

PMID:
42561459
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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