Evaluating Rare Variants in Complex Disorders Using Next-Generation Sequencing

• Type of Material: Article
• Authors: Matthew Ezewudo, Emory University; Michael Zwick, Emory University
• Language: English
• Date: 2013-04
• Publisher: Current Medicine Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013, Springer Science+Business Media New York
• Final Published Version (URL): http://link.springer.com/article/10.1007%2Fs11920-013-0349-4
• Title of Journal or Parent Work: Current Psychiatry Reports
• ISSN: 1523-3812
• Volume: 15
• Issue: 4
• Start Page: 349
• End Page: 349
• Grant/Funding Information: Grant from National Institutes of Health/National Heart, Lung, and Blood Institute (M.E. Zwick)
• Keywords: Psychiatry; Copy number variants; SNVs; CNVs; Complex traits; Autism; Single nucleotide variants; Complex neuropsychiatric disorders; Targeted enrichment; Genetic architecture; Genetic disorders; Single nucleotide polymorphisms; Schizophrenia; Human genetics; SNPs; Next-generation sequencing; Structural variation; Genomics
• Research Categories: Engineering, Biomedical; Biology, Genetics

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.