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

Authors

  • Hyungsuk Kim,

    Corresponding author
    1. National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA
    • Correspondence: Hyungsuk Kim, National Institutes of Health, 9 Memorial Dr B9 Rm 1W121, Bethesda, MD 20892, USA.

      E-mail: kimhy@mail.nih.gov

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  • Elizabeth Crago,

    1. Department of Health Promotion and Development, School of Nursing; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Mirim Kim,

    1. National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA
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  • Paula Sherwood,

    1. Department of Health Promotion and Development, School of Nursing; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Yvette Conley,

    1. Department of Health Promotion and Development, School of Nursing; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Samuel Poloyac,

    1. Department of Health Promotion and Development, School of Nursing; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
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  • Mary Kerr

    1. National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA
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  • Conflict of interest: None declared.
  • Funding: This research was funded by National Institutes of Health.

Abstract

Background

A typology of cerebral vasospasm has been proposed based on distinct clinical manifestations: delayed cerebral ischemia, symptomatic ‘vasospasm’, angiographic vasospasm, and transcranial Doppler 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 Caucasian 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 Doppler vasospasm showed significant genetic association with single nucleotide polymorphism (SNP) (rs999662, P = 3·39 × 10−8). Statistical P-value of rs999662 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 Doppler vasospasm may be an appropriate intermediate but still clinically relevant phenotype for genetic association studies. Association with SNP rs999662 indicates a potential role for the region containing the solute carrier family 12 member 3 (SLC12A3) gene in transcranial Doppler vasospasm following sub-arachnoid hemorrhage.

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