Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population
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Abstract
Objective To construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke.
Methods Using a 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 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (hazard ratio [HR] 1.99, 95% confidence interval [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 lifetime risk as high as 41.1% (95% CI 31.4%–49.5%). 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 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 metaPRS is predictive of stroke risk.
Glossary
- AF=
- atrial fibrillation;
- AHA=
- American Heart Association;
- ARR=
- absolute risk reduction;
- BMI=
- body mass index;
- BP=
- blood pressure;
- CAD=
- coronary artery disease;
- China MUCA 1998=
- China Multicenter Collaborative Study of Cardiovascular Epidemiology 1998;
- China-PAR project=
- Prediction for Atherosclerotic Cardiovascular Disease Risk in China;
- CI=
- confidence interval;
- CIMIC=
- Community Intervention of Metabolic Syndrome in China & Chinese Family Health Study;
- CVH=
- cardiovascular health;
- DBP=
- diastolic blood pressure;
- FBG=
- fasting blood glucose;
- GWAS=
- genome-wide association studies;
- HDL-C=
- high-density lipoprotein cholesterol;
- HR=
- hazard ratio;
- ICD-10=
- International Classification of Diseases, 10th revision;
- IDI=
- integrated discrimination improvement;
- InterASIA=
- International Collaborative Study of Cardiovascular Disease in Asia;
- LD=
- linkage disequilibrium;
- LDL-C=
- low-density lipoprotein cholesterol;
- NRI=
- net reclassification improvement;
- OR=
- odds ratio;
- PRS=
- polygenic risk score;
- SBP=
- systolic blood pressure;
- SNP=
- single-nucleotide polymorphism;
- T2D=
- type 2 diabetes;
- TC=
- total cholesterol
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Class of Evidence: NPub.org/coe
- Received November 10, 2020.
- Accepted in final form May 3, 2021.
- © 2021 American Academy of Neurology
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