Cerebral vasospasm after sub‐arachnoid hemorrhage as a clinical predictor and phenotype for genetic association study

Background A typology of cerebral vasospasm has been proposed based on distinct clinical manifestations: delayed cerebral ischemia, symptomatic ‘vasospasm’, angiographic vasospasm, and transcranial D oppler vasospasm. We examined each distinct clinical manifestation in a nonparametric genetic association study. Aims The purpose of this study was to examine and compare each four distinct acute clinical manifestations and test its perspectives in genetic association studies. Methods Two hundred forty‐five C aucasian patients with sub‐arachnoid hemorrhage were evaluated for these four distinct clinical manifestations along with 906 600 single‐nucleotide polymorphisms across the human genome. Results The four clinical manifestations were significantly associated with each other as P ‐values ranged from 3·31 × 10 −4 to 8·10 × 10 −15 . Transcranial D oppler vasospasm showed significant genetic association with single nucleotide polymorphism ( SNP ) ( rs 999662, P  = 3·39 × 10 −8 ). Statistical P ‐value of rs 999662 in association with delayed cerebral ischemia, symptomatic ‘vasospasm’, and angiographic vasospasm was 0·0017, 0·0017, and 0·19, respectively. Conclusions Despite different criteria for each of the four clinical manifestations, they are significantly associated with each other. Our results suggest transcranial D oppler vasospasm may be an appropriate intermediate but still clinically relevant phenotype for genetic association studies. Association with SNP rs 999662 indicates a potential role for the region containing the solute carrier family 12 member 3 ( SLC12A3 ) gene in transcranial D oppler vasospasm following sub‐arachnoid hemorrhage.