Genome-Wide Polygenic Score for Muscle Strength Predicts Risk for Common Diseases and Lifespan: A Prospective Cohort Study

Abstract

Background: We used a polygenic score for hand grip strength (PGS HGS) to investigate whether genetic predisposition for higher muscle strength predicts age-related noncommunicable diseases, survival from acute adverse health events, and mortality. Methods: This study consisted of 342 443 Finnish biobank participants from FinnGen Data Freeze 10 (53% women) aged 40-108 with combined genotype and health registry data. Associations between PGS HGS and a total of 27 clinical endpoints were explored with linear or Cox regression models. Results: A higher PGS HGS was associated with a reduced risk of selected common noncommunicable diseases and mortality by 2%-10%. The risk for these medical conditions decreased by 5%-23% for participants in the highest PGS HGS quintile compared to those in the lowest PGS HGS quintile. A 1 standard deviation (SD) increase in the PGS HGS predicted a lower body mass index (β = -0.112 kg/m2, standard error [SE] = 0.017, p = 1.69E-11) in women but not in men (β = 0.004 kg/m2, p = .768). PGS HGS was not associated with better survival after acute adverse health events compared to the nondiseased period. Conclusions: The genotype that supports higher muscle strength appears to protect against future health adversities, albeit with modest effect sizes. Further research is needed to investigate whether or how a favorable lifestyle modifies this intrinsic capacity to resist diseases, and if the impacts of lifestyle behavior on health differs due to genetic predisposition for muscle strength.