The clinical utility of a GRS depends on its performance in combination with established risk factors and risk models. To examine this, we conducted analyses integrating information on risk factor levels based on (i) recent ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guidelines34 (SBP < 120 mm Hg); (ii) AHA/ASA guidelines for primary prevention of stroke33 (BMI < 25 kg m−2); (iii) smoking status and diabetes status. We used Cox models of these established risk factors and the metaGRS together with the estimated baseline cumulative hazards to predict cumulative incidence of IS for individuals with a high metaGRS (top 1%), average metaGRS (50%), and low metaGRS (bottom 1%) along with two levels of risk factors: (i) meeting guideline targets for the above risk factors34 and (ii) the following combination of risk factors representative of an individual at typical stroke risk: SBP = 140 mm Hg, BMI = 30 kg m−2, current smoking, and no diagnosed diabetes.
