Joint Effects of GWAS SNPs in Coagulation System Confer Risk to Hypertensive Intracerebral Hemorrhage

Recent genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with coagulation system, including hemostatic factors and hematological phenotypes. However, few articles described the relationships between these SNPs and the risk of hemorrhagic stroke. The aim of our study was to evaluate the roles of these SNPs as risk factors and survival predictors for hemorrhagic stroke. Thirteen SNPs from GWAS in coagulation system were genotyped in a Chinese Han population including 1000 patients with hemorrhagic stroke (intracerebral hemorrhage, ICH = 743; subarachnoid hemorrhage, SAH = 257) and 1044 population-based controls. The associations between the genetics risk score (GRS) and risk of hemorrhagic stroke as well as post-stroke adverse outcomes were determined. No individual SNP was associated with the risk of hemorrhagic stroke. The GRS was calculated by summing the number of risk alleles of each SNP, and a total of 13 SNPs were included. Meanwhile, the GRS cutoffs values were defined to be close to quartiles or tertiles in control subjects. For quartiles, individuals with GRS about 8–9, 10–11, ≥12 had 1.28 (OR 1.28, 95% CI 0.98–1.68, p = 0.067)-, 1.36 (OR 1.36, 95% CI 1.04–1.79, p = 0.026)-, 1.53 (OR 1.53, 95% CI 1.13–2.07, p = 0.006)-fold increase in ICH risk compared to those with GRS ≤7, respectively; for tertiles, individuals with GRS about GRS 9–10, ≥11 had 0.98 (OR 0.98, 95% CI 0.78–1.23, p = 0.067)- and 1.26 (OR 1.26, 95% CI 1.00–1.59, p = 0.048)-fold increase in ICH risk compared to those with GRS ≤8, respectively. Further stratification analyses indicated that this association was only found in hypertensive ICH subjects. However, no statistical difference was found in the volume of hematoma, activities of daily living scale as well as hospital death in the ICH patients based on GRS values. Joint effects of SNPs associated with low coagulation factor levels might confer risk to ICH patients with hypertension. However, the clinical value on risk stratification and survival prediction was limited.