Evaluating Rare Variants in Complex Disorders Using Next-Generation Sequencing

Genetic Disorders (JF Cubells and EB Binder, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Genetic Disorders


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.


Human genetics Genomics Genetic architecture Complex traits Next-generation sequencing Targeted enrichment Single nucleotide variants SNVs Single nucleotide polymorphisms SNPs Structural variation Copy number variants CNVs Complex neuropsychiatric disorders Schizophrenia Autism Genetic disorders Psychiatry 


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.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Human GeneticsEmory UniversityAtlantaUSA

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