Potential key genes for predicting risk of stroke occurrence: A computational approach

Abstract

To investigate prospective key genes and pathways associated with the pathogenesis and prognosis of stroke types along with subtypes. Human genes using genome assembly build 38 patch release 13 with known gene symbols through NCBI gene database (https://www.ncbi.nlm.nih.gov/gene) were fetched. PubMed advanced queries were constructed using stroke-related keywords and associations were calculated using Normalized pointwise mutual information (nPMI) between each gene symbol and queries. Genes related with stroke risk within their types and subtypes were investigated in order to discover genetic markers to predict individuals who are at the risk of developing stroke with their subtypes. A total of 2,785 (9.4%) genes were found to be linked to the risk of stroke. Based on stroke types, 1,287 (46.2%) and 376 (13.5%) genes were found to be related with ischemic stroke (IS) and hemorrhagic stroke (HS) respectively. Further stratification of IS based on TOAST classification, 86 (6.6%) genes were confined to Large artery atherosclerosis; 131 (10.1%) and 130 (10%) genes were related with the risk of small vessel disease and Cardioembolism subtypes of IS. Evidences reported through published meta-analysis and GWAS studies suggested for the association of nine highly associated genes and therefore, we concluded a prognostic panel of nine genes comprising of CYP4A11, ALOX5P, NOTCH, NINJ2, FGB, MTHFR, PDE4D, HDAC9, and ZHFX3 can be treated as a diagnostic marker to predict individuals who are at the risk of developing stroke. Validation of these nine prognostic markers are further required by conducting case-control studies embedded with large sample size.