Joint impact of polygenic risk score and lifestyles on early- and late-onset cardiovascular diseases.

Understanding the interactions between genetic risk and lifestyles on different types and age onsets of cardiovascular disease (CVD) risk can help identify individuals for whom lifestyle changes would be beneficial. Here we developed three polygenic risk scores, called MetaPRSs, for coronary artery disease, ischaemic stroke and intracerebral haemorrhage by combining PRSs for CVD and CVD-related risk factors in 96,400 participants from the prospective China Kadoorie Biobank. Genetic and lifestyle risks were categorized by the disease-specific MetaPRSs and the number of unfavourable lifestyles. High genetic risk and unfavourable lifestyles were found to be more strongly associated with early than late onset of CVD outcomes in men and women. Change from unfavourable to favourable lifestyles resulted in 14.7-, 2.5- and 2.6-fold greater reductions in incidence rates of early-onset coronary artery disease and ischaemic stroke and late-onset coronary artery disease in high than low genetic risk group. Young adults at high genetic risk may have larger benefits in preventing CVD from lifestyle improvements.