Dynamic expression of genes associated with schizophrenia and bipolar disorder across development.

Transl Psychiatry 2019 02 4;9(1):74. Epub 2019 Feb 4.

Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.

Common genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence of significant, but not complete, overlap in genetic risk between the two disorders. It has been hypothesised that genetic variants conferring risk for these disorders do so by influencing brain development, leading to the later emergence of symptoms. The comparative profile of risk gene expression for schizophrenia and bipolar disorder across development over different brain regions however remains unclear. Using genotypes derived from genome-wide associations studies of the largest available cohorts of patients and control subjects, we investigated whether genes enriched for schizophrenia and bipolar disorder association show a bias for expression across any of 13 developmental stages in prefrontal cortical and subcortical brain regions. We show that genetic association with schizophrenia is positively correlated with expression in the prefrontal cortex during early midfetal development and early infancy, and negatively correlated with expression during late childhood, which stabilises in adolescence. In contrast, risk-associated genes for bipolar disorder did not exhibit a bias towards expression at any prenatal stage, although the pattern of postnatal expression was similar to that of schizophrenia. These results highlight the dynamic expression of genes harbouring risk for schizophrenia and bipolar disorder across prefrontal cortex development and support the hypothesis that prenatal neurodevelopmental events are more strongly associated with schizophrenia than bipolar disorder.

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http://dx.doi.org/10.1038/s41398-019-0405-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362023PMC
February 2019
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References

(Supplied by CrossRef)
Article in Arch. Gen. Psychiatry
DR Weinberger et al.
Arch. Gen. Psychiatry 1987
Article in Br. Med. J.
RM Murray et al.
Br. Med. J. 1987
Article in Lancet
MJ Owen et al.
Lancet 2016
Article in Nat. Rev. Neurosci.
R Birnbaum et al.
Nat. Rev. Neurosci. 2017
Article in Transl. Psychiatry
LD Selemon et al.
Transl. Psychiatry 2015
Article in Nature
J Os Van et al.
Nature 2010
Article in Schizophr. Bull.
A Demjaha et al.
Schizophr. Bull. 2012
Article in Lancet
P Jones et al.
Lancet 1994
Article in J. Affect Disord.
C Marangoni et al.
J. Affect Disord. 2016
Article in Arch. Gen. Psychiatry
RA Machón et al.
Arch. Gen. Psychiatry 1997
Article in JAMA Psychiatry
R Parboosing et al.
JAMA Psychiatry 2013

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