APOE ε4 is associated with younger age at ischemic stroke onset but not with stroke outcome.

Stroke outcome is determined by a complex interplay, where age and stroke severity are predominant predictors. Studies on hemorrhagic stroke indicate that APOE genotype is a predictor of poststroke outcomes,(1,2) but results from studies on ischemic stroke are more conflicting.(1,3) There is 1 study suggesting an influence of APOE genotype on age at ischemic stroke onset,(4) and sex-specific effects on outcome have been reported.(5) Taken together, there is a need for larger studies on APOE and ischemic stroke outcomes with integrated information on age, severity, and sex.The 3 common APOE alleles epsilon 2, epsilon 3, and epsilon 4 can be separated by a combination of 2 single nucleotide polymorphisms (SNPs), rs429358 and rs7412. Thus, associations with APOE alleles are not directly captured in a regular genome-wide association study (GWAS), where each SNP is investigated separately. We derived the 3 common APOE alleles and investigated the interplay between APOE, age at ischemic stroke onset, severity, sex, and outcome within a large international collaboration, the Genetics of Ischaemic Stroke Functional Outcome (GISCOME) network.