Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan: evidence from multiple cohort studies
Objective To investigate the associations across genetic and lifestyle factors with lifespan. Design A longitudinal cohort study. Setting UK Biobank. Participants 353 742 adults of European ancestry, who were recruited from 2006 to 2010 and were followed up until 2021. Exposures A polygenic risk score for lifespan with long (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, moderate alcohol consumption, regular physical activity, healthy body shape, adequate sleep duration, and a healthy diet, categorised into favourable, intermediate, and unfavourable lifestyles. Main outcome measures Lifespan defined as the date of death or the censor date minus the date of birth. Results Of the included 353 742 participants of European ancestry with a median follow-up of 12.86 years, 24 239 death cases were identified. Participants were grouped into three genetically determined lifespan categories including long (20.1%), intermediate (60.1%), and