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Evaluating Rare Variants in Complex Disorders Using Next-Generation Sequencing

  • Genetic Disorders (JF Cubells and EB Binder, Section Editors)
  • Published:
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Abstract

Determining the genetic architecture of liability for complex neuropsychiatric disorders like autism spectrum disorders and schizophrenia poses a tremendous challenge for contemporary biomedical research. Here we discuss how genetic studies first tested, and rejected, the hypothesis that common variants with large effects account for the prevalence of these disorders. We then explore how the discovery of structural variation has contributed to our understanding of the etiology of these disorders. The rise of fast and inexpensive oligonucleotide sequencing and methods of targeted enrichment and their influence on the search for rare genetic variation contributing to complex neuropsychiatric disorders is the next focus of our article. Finally, we consider the technical challenges and future prospects for the use of next-generation sequencing to reveal the complex genetic architecture of complex neuropsychiatric disorders in both research and the clinical settings.

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Conflict of Interest

M. Ezewudo: none; M.E. Zwick: grant from National Institutes of Health/National Heart, Lung, and Blood Institute, and consultant to Henry M. Jackson Foundation.

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  1. Department of Human Genetics, Emory University, Whitehead Biomedical Research Building, Suite 301, Atlanta, GA, 30322, USA

    Matthew Ezewudo & Michael E. Zwick

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  1. Matthew Ezewudo
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  2. Michael E. Zwick
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Correspondence to Michael E. Zwick.

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This article is part of the Topical Collection on Genetic Disorders

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Ezewudo, M., Zwick, M.E. Evaluating Rare Variants in Complex Disorders Using Next-Generation Sequencing. Curr Psychiatry Rep 15, 349 (2013). https://doi.org/10.1007/s11920-013-0349-4

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