Genetic Disorders (JF Cubells and EB Binder, Section Editors)

Current Psychiatry Reports

, 15:333

Detecting Rare Variants for Psychiatric Disorders Using Next Generation Sequencing: A Methods Primer

  • Andre AltmannAffiliated withDepartment of Neurology & Neurological Sciences, Functional Imaging in Neurodegenerative Disorders Laboratory, Stanford University Email author 
  • , Carina QuastAffiliated withMax Planck Institute of Psychiatry, Molecular Genetics of Affective Disorder
  • , Peter WeberAffiliated withMax Planck Institute of Psychiatry, Molecular Genetics of Affective Disorder

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Abstract

Recent advances in massively parallel sequencing (MPS) have had an extensive impact on research in medical genomics. In particular, the analysis of rare variants using MPS promises to lead to a better understanding of complex disorders. Nevertheless, for meaningful studies that address the genetic basis for neuropsychiatric disorders, at least hundreds of patient samples have to be analyzed. This undertaking is still not feasible for single research groups on a whole-genome scale and in individual samples. Thus, researchers increasingly employ strategies for reducing the amount of sequencing efforts, such as target enrichment and non-barcoded sample pooling. This review provides an overview of current technologies, discusses options for reduced experimental designs, and illustrates the successful application of the presented methodologies in a recent study of panic disorder patients. Thereby, it aims to introduce the emerging field of MPS into neuropsychiatric research and might serve as a guide for further studies.

Keywords

Next-generation sequencing NGS Massively parallel sequencing MPS Targeted re-sequencing Target enrichment Exome enrichment Sample pooling DNA pooling Rare genetic variants Bioinformatics Complex disease Psychiatric disorder Anxiety disorder Panic disorder Human genetics Genetic disorders Genome-wide association studies GWAS Example study Review Psychiatry