Genome-wide polygenic risk score for muscle strength predicts lower risk for common diseases and longer life span among the Finnish population: a prospective population based cohort study of the 342 443 FinnGen participants

ABSTRACT Purpose To use a genome-wide polygenic risk score for hand grip strength (PRS HGS) to investigate whether the muscle strength genotype predicts the most common age related noncommunicable diseases, survival from acute adverse health events, and all cause 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 were explored with a linear or Cox proportional hazards regression models. Results A higher PRS HGS predicted a lower body mass index (BMI) (β = −0.112 kg/m 2 , standard error (SE) = 0.017, P = 1.69 × 10 −11 ) in women but not in men (β = 0.004 kg/m 2 , P = 0.768, sex by PRS HGS interaction: P = 2.12 × 10 −07 ). In all participants, a higher PRS HGS was associated with a lower risk for obesity diagnosis (hazard ratio 0.94, 95% confidence interval 0.93 to 0.95), type 2 diabetes (0.95, 0.94 to 0.96), ischemic heart diseases (0.97, 0.96 to 0.97), hypertension (0.97, 0.96 to 0.97), stroke (0.97, 0.96 to 0.98), asthma (0.94, 0.93 to 0.95), chronic obstructive pulmonary disease (0.94, 0.92 to 0.95), polyarthrosis (0.90, 0.88 to 0.92), knee arthrosis (0.98, 0.97 to 0.99), rheumatoid arthritis (0.95, 0.94 to 0.97), osteoporosis (0.95, 0.93 to 0.97), falls (0.98, 0.98 to 0.99), depression (0.95, 0.94 to 0.96), and vascular dementia (0.93, 0.89 to 0.96). In women only, a higher PRS predicted a lower hazard for any dementia (0.94, 0.92 to 0.96) and Alzheimer’s disease (0.96, 0.93 to 0.98). Participants with a higher PRS HGS had a decreased risk of cardiovascular (0.96, 0.95 to 0.98) and all cause mortality (0.97, 0.96 to 0.98). However, the predictive value of the PRS HGS for mortality was not pronounced after adverse acute health events compared to the non-diseased period. Conclusions The genotype that supports higher muscle strength protects against many future health adversities. 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 polygenic risk.