Familial risk of carpal tunnel syndrome among first-degree relatives and interaction with obesity and hyperglycemia - A population-based study in Korea

Although genetic and lifestyle factors are known to be involved in carpal tunnel syndrome development, population-level familial risk and interactions between gene and environmental factors have been scarcely studied. We investigated population-based familial risk and assessed the interactions between family history and obesity or hyperglycemia. By using the National Health Insurance database, which covers the total population in Korea, we constructed a cohort of 5,524,403 individuals with information on familial relationships and lifestyle factors from 2002 to 2019. Familial risk was calculated using hazard ratios (HRs) that compare the risk of individuals with and without affected first-degree relatives (FDRs). Interactions between familial risk and obesity/hyperglycemia were assessed on an additive scale using the relative excess risk due to interaction (RERI). Individuals with affected FDRs showed a 1.99-fold increased risk of disease, with twin, brother, sister, paternal, and maternal risks (95% confidence interval) of 17.53 (9.43-32.58), 2.57 (2.20-3.00), 2.38 (2.04-2.77), 1.72 (1.60-1.86), and 1.95 (1.88-2.03), respectively. In the interaction analysis, the combined risk of positive family history and high body mass index or hyperglycemia exceeded the sum of their individual risks (HR 3.33 vs 2.55, 2.51 vs 2.28, respectively), showing statistically significant interactions (RERI 0.78, 0.23, respectively). Obese individuals with a family history (RERI 1.12) showed a more prominent interaction than overweight individuals (RERI 0.26), and similarly, excess risk was higher in severe hyperglycemic (RERI 0.82) compared with moderate hyperglycemic individuals (RERI 0.28), suggesting a dose-response interaction pattern. Our interaction findings indicate that individuals with a family history and obesity/hyperglycemia should be considered a high-risk population.