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Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

Molecular Psychiatry volume 16, pages 452–461 (2011)Cite this article

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Abstract

Cytoarchitectural abnormalities have been described in the prefrontal cortex (PFC) of subjects with psychiatric disorders. We explored the possible genetic causalities that may underlie the cytoarchitectural abnormalities of calbindin-containing γ-aminobutyric acid (GABA)ergic neurons and perineuronal oligodendrocytes in the PFC of subjects with psychiatric disorders by converging results from genome-wide single-nucleotide polymorphism (SNP) scans for the traits and expression SNP (eSNP) associations. In the initial genome-wide scans, we identified several development- and apoptosis-related genes associated with the cytoarchitectural traits. Moreover, the susceptibility gene for bipolar disorder, PPP2R2C, was found to be associated with the number of perineuronal oligodendrocytes. Further eSNP analyses indicated that two novel candidate genes, RAB2A and SLC38A1, were associated with the density of calbindin-positive neurons and the number of perineuronal oligodendrocytes, respectively. Our findings may provide novel insights into the genetic causalities associated with cytoarchitectural abnormalities in the PFC of subjects with major psychiatric disorders as well as into the etiology of such disorders.

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Acknowledgements

We thank all the investigators generating original data in the SMRIDB, in particular Drs Natalya Uranova, Gavin Reynolds, Anthony Altar, Sabine Bahn, Tadafumi Kato and Chunyu Liu, along with their many collaborators, who made this study possible.

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  1. Stanley Brain Research Laboratory, Stanley Medical Research Institute, Rockville, MD, USA

    S Kim & M J Webster

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Correspondence to S Kim.

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Kim, S., Webster, M. Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders. Mol Psychiatry 16, 452–461 (2011). https://doi.org/10.1038/mp.2010.23

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