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Review
. 2017 Jul;14(3):564-581.
doi: 10.1007/s13311-017-0551-x.

Genetic Approaches to Understanding Psychiatric Disease

Jacob J Michaelson  1   2   3   4   5   6   7
Affiliations
Review

Genetic Approaches to Understanding Psychiatric Disease

Jacob J Michaelson. Neurotherapeutics. 2017 Jul.

Abstract

Human genetic studies have been the driving force in bringing to light the underlying biology of psychiatric conditions. As these studies fill in the gaps in our knowledge of the mechanisms at play, we will be better equipped to design therapies in rational and targeted ways, or repurpose existing therapies in previously unanticipated ways. This review is intended for those unfamiliar with psychiatric genetics as a field and provides a primer on different modes of genetic variation, the technologies currently used to probe them, and concepts that provide context for interpreting the gene-phenotype relationship. Like other subfields in human genetics, psychiatric genetics is moving from microarray technology to sequencing-based approaches as barriers of cost and expertise are removed, and the ramifications of this transition are discussed here. A summary is then given of recent genetic discoveries in a number of neuropsychiatric conditions, with particular emphasis on neurodevelopmental conditions. The general impact of genetics on drug development has been to underscore the extensive etiological heterogeneity in seemingly cohesive diagnostic categories. Consequently, the path forward is not in therapies hoping to reach large swaths of patients sharing a clinically defined diagnosis, but rather in targeting patients belonging to specific "biotypes" defined through a combination of objective, quantifiable data, including genotype.

Keywords: GWAS; Psychiatric genetics; copy number variant; microarrays; sequencing.

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Figures

Fig. 1
Fig. 1
Size distributions of classes of genetic variation, and the ability of microarray and sequencing technology to detect them. Solid circle = routinely detectable; (+) = detectable depending on platform, or with special protocols, or with limitations on size or coverage; (–) = not detectable; SNP = single-nucleotide polymorphism; SNV = single nucleotide variant; indel = insertion/deletion; STR = short tandem repeat; VNTR = variable number tandem repeat; SV = structural variant; CNV = copy number variant
See this image and copyright information in PMC

References

    1. Kurahashi H, Tsutsumi M, Nishiyama S, Kogo H, Inagaki H, Ohye T. Molecular basis of maternal age-related increase in oocyte aneuploidy. Congenit Anom (Kyoto) 2012;52(1):8–15. doi: 10.1111/j.1741-4520.2011.00350.x. - DOI - PubMed
    1. Jiang J, Jing Y, Cost GJ, et al. Translating dosage compensation to trisomy 21. Nature. 2013;500(7462):296–300. doi: 10.1038/nature12394. - DOI - PMC - PubMed
    1. Antonarakis SE. Down syndrome and the complexity of genome dosage imbalance. Nat Rev Genet. 2017;18(3):147–163. doi: 10.1038/nrg.2016.154. - DOI - PubMed
    1. Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ. Schizophrenia and affective disorders—cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Am J Hum Genet. 2001;69(2):428–433. doi: 10.1086/321969. - DOI - PMC - PubMed
    1. Alkan C, Coe BP, Eichler EE. Genome structural variation discovery and genotyping. Nat Rev Genet. 2011;12(5):363–376. doi: 10.1038/nrg2958. - DOI - PMC - PubMed