Genetic risk, muscle strength and risk of incident major depressive disorder: results from the UK Biobank

Background Genetic factors and muscle strength both contribute to the risk of major depressive disorder (MDD), but whether high muscle strength can offset the risk of MDD with different genetic risk is unknown. This study aims to examine whether a higher muscle strength is associated with lower risk of MDD regardless of genetic risk among middle-aged and older adults. Methods This cohort study obtained data from the UK Biobank, which includes 345,621 individuals aged 40-69 years (mean (standard deviation): 56.7 (7.99) years) without baseline MDD. Polygenic risk score for MDD was categorised as low, intermediate or high. The mean of the right- and left-hand grip strength values was used in the analysis and was divided into three categories. Results 9,753 individuals developed MDD within 2,752,461 person-years of follow-up. The multivariable adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of MDD across increased grip strength categories were 1.00, 0.72 (0.68-0.75) and 0.56 (0.53-0.59) (P for trend <0.0001). The HRs (95% CIs) of incident MDD across the genetic risk categories were 1.00, 1.11 (1.05-1.17) and 1.20 (1.13-1.28) (P for trend <0.0001); 4.07% of individuals with a high genetic risk and low grip strength developed MDD, and 1.72% of individuals with a low genetic risk and high grip strength developed MDD, with an HR (95% CI) of 0.44 (0.39-0.50). Conclusions Both muscle strength and genetic risk were significantly associated with incident MDD. A higher muscle strength was associated with a lower MDD risk among individuals with a high genetic risk. Improving muscle strength should be encouraged for all individuals, including individuals with high genetic risk for MDD.