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Cross-Disorder Psychiatric Genomics


Purpose of Review

The following review provides some description of the movement in cross-disorder psychiatric genomics toward addressing both comorbidity and polygenicity.

Recent Findings

We attempt to show how dimensional approaches to the phenotype have led to further addressing the problem of comorbidity of psychiatric diagnoses. And we also attempt to show how a dimensional approach to the genome, with different statistical methods from traditional genome-wide association analyses, has begun to resolve the problem of massive polygenicity.


Cross-disorder research, of any area in psychiatry, arguably has the most potential to inform clinical diagnosis, early detection and prevention strategies, and pharmacological treatment research. Future research might leverage what we now know to inform developmental studies of risk and resilience.

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  1. 1.

    General effects of co-heritability between specific disorders found in these analyses have withstood a recent, more sophisticated statistical approach to controlling for linkage disequilibrium, LD Score Regression (7.Bulik-Sullivan B, Finucane HK, Anttila V, Gusev A, Day FR, Consortium R, et al. An Atlas of Genetic Correlations across Human Diseases and Traits2015 2015-01-01 00:00:00.).

  2. 2.

    It is important to note, however, that “synaptic function” is a very broad category in the biological pathway literature, and that psychiatric diagnoses are likely all related to synaptic function to some degree. In addition, there may be unique forms of ASD and psychosis corresponding to earlier onset or increased genetic risk, and these regions could be associated with specific forms of illness that are not broadly generalizable.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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    Schizophrenia Working Group of the Psychiatric Genomics C. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421–7. Finding genetic effects on massively polygenic disorders has required genome-wide association studies (GWAS) with tens of thousands of samples. This set of schizophrenia findings from the PGC is a major boon for psychiatric genetics, and the polygenic weights from these samples provide important information about biological mechanisms affecting liability.

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    Bulik-Sullivan B, Finucane HK, Anttila V, Gusev A, Day FR, Consortium R, et al. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47(11):1236–41. The field is quickly developing and validating strategies to examine the additive effects of genetic variants across genes, pathways, and larger swathes of the genome. This important application involved polygenic profile scoring of traits using GWAS summary statistics, deriving genomic relatedness matrices to calculate heritability estimates from common genetic variants, and modeling the linkage disequilibrium in the sample in order to obtain more accurate estimates of genetic risk.

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    Consortium TP, Akbarian S, Liu C, Knowles JA, Vaccarino FM, Farnham PJ, et al. The PsychENCODE project. Nat Neurosci. 2015;18(12):1707–12. In the near future, the PsychENCODE project aims to produce a public resource of multidimensional genomic data using tissue- and cell type–specific samples from approximately 1,000 phenotypically well-characterized, high-quality healthy and disease-affected human post-mortem brains. This research begins with a focus on ASD, BP, and SZ, and will examine the coheritability of these disorders. These highly anticipated analyses could further elucidate biological mechanisms underlying pleiotropy in psychiatric illness.

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Correspondence to Anna R. Docherty.

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Dr. Anna R. Docherty, Dr. Arden A. Moscati, and Dr. Ayman H. Fanous declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Genetics and Neuroscience

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Docherty, A.R., Moscati, A.A. & Fanous, A.H. Cross-Disorder Psychiatric Genomics. Curr Behav Neurosci Rep 3, 256–263 (2016). https://doi.org/10.1007/s40473-016-0084-3

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  • Cross-disorder
  • Genetic
  • GWAS
  • Psychiatric Genomics Consortium
  • Pleiotropy
  • Co-heritability
  • Comorbidity