Supplemental data for: Development and validation of a polygenic risk score for stroke in the Chinese population

Objective: To construct a polygenic risk score (PRS) for stroke and
evaluate its utility in risk stratification and primary prevention for
stroke.   Methods: Using meta-analytic approach and large
genome-wide association results for stroke and stroke-related traits in
East Asians, we generated a combined PRS (metaPRS) by incorporating 534
genetic variants in a training set of 2,872 patients with stroke and 2,494
controls. We then validated its association with incident stroke using Cox
regression models in large Chinese population-based prospective cohorts
comprising 41,006 individuals.   Results: During a total of
367,750 person-years (mean follow-up 9.0 years), 1,227 participants
developed stroke before age of 80 years. Individuals with high polygenic
risk had an about 2-fold higher risk of incident stroke compared with
those with low polygenic risk (HR: 1.99, 95% CI: 1.66-2.38), with the
lifetime risk of stroke being 25.2% (95% CI: 22.5%-27.7%) and 13.6% (95%
CI: 11.6%-15.5%), respectively. Individuals with both high polygenic risk
and family history displayed the lifetime risk as high as 41.1% (95% CI:
31.4%-49.5%). Moreover, individuals with high polygenic risk achieved
greater benefits in terms of absolute risk reductions from adherence to
ideal fasting blood glucose and total cholesterol than those with low
polygenic risk. Maintaining favorable cardiovascular health (CVH) profile
could substantially mitigate the increased risk conferred by high
polygenic risk to the level of the low polygenic risk (from 34.6 % to
13.2%).   Conclusions: Our metaPRS has great potential for risk
stratification of stroke and identification of individuals who may benefit
more from maintaining ideal CVH.    Classification of
Evidence: This study provides Class I evidence that a meta-polygenic risk
score is predictive of stroke risk.