Abstract WMP99: Proteomics Study Of Stroke In Young Adults

Introduction: A prior systematic Mendelian randomization screen of 653 circulating proteins in a predominantly older ischemic stroke (IS) population identified a causal role for several established and novel biomarkers for IS and IS subtypes. We contrasted the magnitude of genetically determined levels of 6 of these biomarkers between early- and late-onset IS. Methods: We constructed genetic risk scores (GRS) for these 6 protein biomarkers from previously published GWAS analyses carried out in European populations. Using regression analysis, we evaluated associations of these GRS with IS and IS subtypes in 10,549 early onset (ages 18-59) and 9,272 late onset (ages 60 and older) IS cases and associated controls. The Wald test was used to test for heterogeneity in the odds ratios between the two groups. Results: Of the 6 biomarkers, only genetically determined protein levels of histo-blood group ABO system transferase were more strongly associated with early compared to late onset stroke (p < 0.002). Higher genetically determined levels of F11 and LPA and lower genetically determined levels of MMP12 were associated with both early and late onset IS with no evidence for differential effect sizes, while genetically determined levels of CD40 and SCARA5 showed no association with either early or late onset stroke. In subtype-specific analyses, increasing levels of genetically determined F11 were correlated with increased risk of all strokes in both groups. Higher genetically determined LPA levels were associated with large artery atherosclerotic (LAA) strokes in both groups, while lower genetically determined MMP12 levels were associated with LAA strokes in both groups. Conclusions: Genetically determined histo-blood group ABO system transferase levels are more strongly associated with all strokes in early than in late onset stroke. Genetically determined blood protein levels of F11, LPA, and MMP12 were associated with both early and late onset stroke. Lack of association for CD40 and SCARA5 may be due to a smaller sample size than the initial discovery study.