Association between frailty and gout in middle-aged and older adults: A nationwide cross-sectional and Mendelian randomization study

With the aging population, frailty is becoming increasingly prevalent among older adults, yet its association with gout, a common form of arthritis affecting middle-aged and older adults, remains unclear. This study investigated the frailty-gout relationship through a nationwide cross-sectional analysis combined with Mendelian randomization (MR). Data from 22,324 adults aged 40 and above in the National Health and Nutrition Examination Survey (NHANES, 2007-2018) were analyzed utilizing survey-weighted logistic regression models. Genome-wide association study data from UK Biobank, TwinGen, and FinnGen were utilized to explore genetic correlations and causality. The cross-sectional study indicated a significant relationship between pre-frail (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.76-3.08, P < .0001) and frail (OR = 4.63, 95% CI = 3.67-5.84, P < .0001) individuals and gout. This association persisted after comprehensive covariate adjustment (pre-frail OR = 2.13, 95% CI = 1.59-2.85, P < .0001; frail OR = 4.11, 95% CI = 3.16-5.35, P < .0001). The interaction effect between frailty and gout was significantly influenced by race/ethnicity (P interaction = .0046) and gender (P interaction = 6.72 × 10-6). Linkage disequilibrium score regression analysis demonstrated a moderate yet significant genetic correlation between the frailty index and gout (rg = 0.319, standard error (SE) = 0.042, P = 2.19 × 10-14). MR analysis confirmed a causal link between frailty index and gout (OR = 2.29, 95% CI = 1.45-3.62, P < .001), while reverse MR analysis indicated no causality. These findings elucidated frailty as a risk factor for gout, underscoring the necessity for uric acid monitoring to mitigate gout risk in frail individuals, potentially informing sustained healthcare initiatives for gout in middle-aged and older adults.