The Joint Effects Of Cardiovascular Disease Related Snps On Ischemic Stroke

Objectives: Previous studies have revealed multiple common variants associated with known risk factors for cardiovascular disease (CVD). Ischemic stroke (IS) and CVD share several risk factors with each having substantial heritability. We aimed to generate a multi-locus genetic risk score (GRS) for ischemic stroke based on CVD related SNPs to evaluate their joint effects on ischemic stroke. Methods: A total of 851 patients and 977 controls were selected from Beijing, Tianjin, Shandong, Shanxi, Shaanxi and Heilongjiang communities. The candidate genes were genotyped by PCR-hybridization. Information about demographic factors, history of disease (such as hypertension), and lifestyle was obtained using structured questionnaires. A GRS model weighted by the absolute value of regression coefficient β was established to comprehensively assess the association between candidate SNPs and ischemic stroke. Using the area under the receiver operating characteristic curve (AUC) to evaluate the value of GRS on predicting ischemic stroke. Results: The GRS of cases was 2.96 ± 0.30, which was significantly higher than controls’ GRS (2.86 ± 0.32) (P < 0.000). With the increase of the GRS, the risk of ischemic stroke became higher (Ptrend < 0.000). Subjects in the top quartile of the GRS had about 2-fold increased risk of ischemic stroke compared with subjects in the lowest quartile (OR adjusted = 1.940, 95%CI = 1.487–2.532, P < 0.000). The AUC = 0.582, P < 0.000. 14 CVD related SNPs had joints effects on ischemic stroke. Conclusion: The GRS of cases was significantly higher than controls’ GRS. As the GRS increased, the risk of ischemic stroke increased. The GRS model has some value for the prediction of ischemic stroke.