The combined effects of cardiovascular disease related SNPs on ischemic stroke

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 IS based on CVD related SNPs to evaluate their combined effects on IS.

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 IS. Using the area under the receiver operating characteristic curve (AUC) to evaluate the value of GRS on predicting IS.

The GRS of cases was 2.87 ± 0.28, which was significantly higher than controls' GRS (2.78 ± 0.30) (P < 0.000). With the increase of the GRS, the risk of IS became higher (P_trend < 0.000). Subjects in the top quartile of the GRS had about 1.9-fold increased risk of IS compared with subjects in the lowest quartile (OR _adjusted = 1.880, 95%CI = 1.442-2.452, P < 0.000). The AUC = 0.580, P < 0.000.

13 CVD related SNPs had combined effects on IS. The GRS of cases was significantly higher than controls' GRS. As the GRS increased, the risk of IS increased. The GRS model has some value for the prediction of IS.