Medicine · Nov 6, 2026

Adult-onset Still’s disease and sarcopenia-related traits – muscle mass, strength, and function: A bi-directional Mendelian randomization study

By Wang J, Peng P, Wang Y et al.

The causal relationship between adult-onset Still’s disease (AOSD) and sarcopenia remains unclear. Therefore, we employed Mendelian randomization (MR) to investigate the causal link between these 2 conditions. This study investigated the causal relationships between AOSD (n = 201,947) and sarcopenia-related traits, including low handgrip strength (n = 256,523), left handgrip strength (n = 406,552), right handgrip strength (n = 461,089), appendicular lean mass (ALM, n = 450,243), and walking pace (WP, n = 459,915). In the first stage, AOSD served as the exposure variable, while the sarcopenia-related traits treated as the outcome variables; in the second stage, the roles were reversed. MR analysis employed inverse variance-weighted, weighted median, weighted mode, and MR-Egger methods. Cochran’s Q statistic was used to assess heterogeneity, while MR-Egger regression and MR-PRESSO were utilized to evaluate pleiotropy. The robustness of the findings, risk of bias, and causal direction were assessed using leave-one-out analysis, funnel plots, and R ² statistics. AOSD may contribute to reduced muscle mass and strength, but not to impaired muscle function. Genetically predicted AOSD is causally associated with reduced ALM (odds ratio [OR] = 0.971, 95% confidence interval [CI]: 0.951–0.991; P = .005) and increased risk of low hand grip strength in individuals over 60 (OR = 1.046, 95% CI: 1.001–1.091; P = .048). It also reduces left hand grip strength (OR = 0.984, 95% CI: 0.976–0.992; P < .001), with no significant effect on right hand grip strength (OR = 0.995, 95% CI: 0.987–1.003; P = .240). with no effect on WP is also observed (OR = 0.994, 95% CI: 0.988–1.001; P = .080). Genetically predicted sarcopenia-related traits (ALM and bilateral grip strength) had no robust causal effect on AOSD. While inverse variance-weighted suggested nominally significant associations of reduced grip strength (≥60 years) and slower WP with AOSD, these results were inconsistent across MR methods and warrant cautious interpretation. AOSD leading to a decline in muscle mass, strength However, it does not significantly affect muscle function, whereas most sarcopenia-related traits showed no convincing causal effect on AOSD. Nominally significant associations observed for low hand grip strength in participants over 60 years and WP were not robust across sensitivity analyses and await further validation.

doi.org/10.1097/md.0000000000051440 Open access PubMed 42994901 Mechanisms