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Genetics of psychiatric disorders in the GWAS era: an update on schizophrenia

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Abstract

The influence of genetic factors in the development of schizophrenia has been convincingly demonstrated by family, twin, and adoption studies. The statistical construct of heritability is generally used for estimating the liability due to genetic factors. Heritability estimates for schizophrenia are reported to be between 60 and 80 %. Due to the technical achievements in whole genome-wide association studies, dissection of the underlying genetic factors was intensified recently, resulting in the conclusion that schizophrenia is essentially a polygenic, complex disorder. Most likely more than 100 genes, each with small effect size, contribute to disease risk. A most recent multi-stage genome-wide association study (Ripke et al. in Nat Genet 2013) identified 22 risk loci and estimated that 8,300 independent single-nucleotide polymorphisms contributed to the risk accounting collectively for 32 % in liability. In addition to this polygenic, complex inheritance, there is also strong indication that in some patients a deletion or insertion of a larger chromosomal region [so-called copy number variation (CNV)] might play a crucial role in pathogenesis. This could be specifically important in sporadic cases with schizophrenia, since a higher frequency of de novo mutations has been associated with these CNVs. Further studies, combining much larger sample sizes as well as application of newer technology, such as deep sequencing technologies will be necessary in order to obtain a more comprehensive understanding of the genetic foundations of schizophrenia.

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Conflict of interest

The authors declare that they have no conflict of interest.

This article is part of the supplement “Bridging the gap between Neurobiology and Psychosocial Medicine.” This supplement was not sponsored by outside commercial interests. It was funded by the German Association for Psychiatry and Psychotherapy (DGPPN).

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Sibylle G. Schwab

  2. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Australia

    Dieter B. Wildenauer

  3. Centre for Clinical Research in Neuropsychiatry, Graylands Hospital, Claremont, Australia

    Dieter B. Wildenauer

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Correspondence to Sibylle G. Schwab.

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Schwab, S.G., Wildenauer, D.B. Genetics of psychiatric disorders in the GWAS era: an update on schizophrenia. Eur Arch Psychiatry Clin Neurosci 263 (Suppl 2), 147–154 (2013). https://doi.org/10.1007/s00406-013-0450-z

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