Abstract P663: Polygenic Risk Scores for Plasma Levels of Fibrin D-Dimer and Tissue Plasminogen Activator Are Associated With Non-Lacunar Stroke

Abstract

Introduction: Plasma concentrations of prothrombotic factors such as fibrinogen have previously been associated with ischemic stroke risk. To extend this observation, we examined the association of polygenic risk scores (PRS) for increased plasma levels of thrombosis-related factors with ischemic stroke. Our hypotheses were that these PRS would be more associated with early than late onset stroke and with non-lacunar than lacunar stroke. Methods: We identified 9053 late onset (≥ 60 years) stroke cases from the NINDS International Stroke Genetics Consortium (SiGN) with 24804 controls and 6594 early onset (< 60 years) stroke cases from the Genetics of Early Onset Ischemic Stroke Consortium with 30561 controls. We identified previously known loci associated with plasma levels of four thrombosis-related factors: fibrinogen, fibrin D-dimer, tPA and PAI-1 from prior GWAS studies and developed genome-wide PRS for plasma concentrations of these factors. We then used logistic regression to test the association of these scores with risk of stroke and stroke subtype. Results: PRS for fibrin D dimer levels were associated with increased risk for all stroke and specifically for older (p = 0.019), but not younger (p = 0.22) onset stroke. PRS for tPA levels were also marginally associated with older (p = 0.06), but not younger (p = 0.24) onset stroke. Genetic risk scores for both D dimer and tPA were associated with non-lacunar stroke (Table 1). Further analyses stratified by age revealed PRS for D dimer to be significantly associated with non-lacunar stroke (but not lacunar stroke) in both late and early onset cohorts. PRS for fibrinogen and PAI-1 were not associated with stroke. Conclusion: Genomic risk scores for thrombosis-related factors including D dimer and tPA levels were associated with risk for ischemic stroke, and specifically, non-lacunar stroke.