Evaluating Rare Variants in Complex Disorders Using Next-Generation Sequencing

• Authors: Matthew Ezewudo, Emory University; Michael Zwick, Emory University
• Journal Title: Current Psychiatry Reports
• Volume: Volume 15, Number 4
• Publisher: Current Medicine Group | 2013-04, Pages 349-349
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s11920-013-0349-4
• Subjects: Biology, Genetics; Engineering, Biomedical
• Keywords: 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

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.