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Structural genomic variation in ischemic stroke

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Abstract

Technological advances in molecular genetics allow rapid and sensitive identification of genomic copy number variants (CNVs). This, in turn, has sparked interest in the function such variation may play in disease. While a role for copy number mutations as a cause of Mendelian disorders is well established, it is unclear whether CNVs may affect risk for common complex disorders. We sought to investigate whether CNVs may modulate risk for ischemic stroke (IS) and to provide a catalog of CNVs in patients with this disorder by analyzing copy number metrics produced as a part of our previous genome-wide single-nucleotide polymorphism (SNP)-based association study of ischemic stroke in a North American white population. We examined CNVs in 263 patients with ischemic stroke (IS). Each identified CNV was compared with changes identified in 275 neurologically normal controls. Our analysis identified 247 CNVs, corresponding to 187 insertions (76%; 135 heterozygous; 25 homozygous duplications or triplications; 2 heterosomic) and 60 deletions (24%; 40 heterozygous deletions; 3 homozygous deletions; 14 heterosomic deletions). Most alterations (81%) were the same as, or overlapped with, previously reported CNVs. We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study.

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Authors and Affiliations

  1. Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA

    Mar Matarin, Javier Simon-Sanchez, Sonja Scholz, Dena G. Hernandez, Angela Britton & Andrew B. Singleton

  2. Unitat de Genética Molecular, Departamento de Genómica y Proteómica, Instituto de Biomedicina de Valencia-CSIC, 46010, Valencia, Spain

    Javier Simon-Sanchez

  3. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Dr, Bethesda, MD, 20892, USA

    Hon-Chung Fung, Cynthia Crews, Fabienne Wavrant De Vrieze & Andrew B. Singleton

  4. Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, Taiwan

    Hon-Chung Fung

  5. Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, London, UK

    Hon-Chung Fung & John A. Hardy

  6. Computational Biology Core, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA

    J. Raphael Gibbs

  7. Section on Biostatistics, Division of Public Health Sciences, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, 27157-1063, USA

    L. Douglas Case

  8. Department of Neurology, Mayo Clinic, Jacksonville, FL, 32256, USA

    Thomas G. Brott & James F. Meschia

  9. Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA

    Robert D. Brown Jr.

  10. Departments of Neurology and Public Health Sciences, University of Virginia, Charlottsville, VA, 22908, USA

    Bradford B. Worrall

  11. Department of Neurology, University of Florida College of Medicine, Jacksonville, FL, 32256, USA

    Scott Silliman

  12. Center for Public Health Genomics, University of Virginia, Charlottsville, VA, 22908, USA

    Stephen S. Rich & Andrew B. Singleton

Authors
  1. Mar Matarin
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  2. Javier Simon-Sanchez
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  3. Hon-Chung Fung
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  4. Sonja Scholz
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  5. J. Raphael Gibbs
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  6. Dena G. Hernandez
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  7. Cynthia Crews
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  8. Angela Britton
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  9. Fabienne Wavrant De Vrieze
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  10. Thomas G. Brott
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  13. Scott Silliman
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  14. L. Douglas Case
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  15. John A. Hardy
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  16. Stephen S. Rich
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  17. James F. Meschia
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  18. Andrew B. Singleton
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Corresponding author

Correspondence to Andrew B. Singleton.

Additional information

Mar Matarin, Javier Simon-Sanchez, Hon-Chung Fung, Sonja Scholz and J Raphael Gibbs contributed equally to this article.

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Matarin, M., Simon-Sanchez, J., Fung, HC. et al. Structural genomic variation in ischemic stroke. Neurogenetics 9, 101–108 (2008). https://doi.org/10.1007/s10048-008-0119-3

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