Our approach shows, for different genomic risk backgrounds, how modifiable risk factors could, in principle, be tailored to an individual’s ability to reduce an established risk factor(s) while maintaining an overall acceptable level of absolute risk. Similarly, this approach could potentially be used to guide early prevention of stroke: identifying individuals at increased risk early in life, who would then be targeted for more intensive lifestyle modifications, similar to the roles that have been proposed for genetics in cancer risk stratification38. Unlike most established risk factors which may vary over time and are typically not informative at an early age, the metaGRS remains stable and can be derived from birth. Later in life, when measurements of established risk factors are available, these can be further combined with the metaGRS to give the most accurate prediction of a person’s risk of incident stroke. Further research is required to determine what levels of risk factor reductions will be achievable and cost effective in practice.
