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 to 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% to 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 one standard deviation (SD) increase in the PGS HGS predicted a lower body mass index (BMI) (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 = 0.768). PGS HGS was not associated with better survival after acute adverse health events compared to the non-diseased 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 favourable lifestyle modifies this intrinsic capacity to resist diseases, and if the impacts of lifestyle behaviour on health differ due to genetic predisposition for muscle strength.