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Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

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Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

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Erratum in: Corrigendum: Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. [Nat Neurosci. 2015]
Astrid M Vicente - Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium
Disponível em texto integral em: http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25599223/

Keywords

Perturbações do Desenvolvimento Infantil e Saúde Mental Genome-wide Association Studies GWAS Psychiatric Disorders

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Citation

Nat Neurosci. 2015 Feb;18(2):199-209. doi: 10.1038/nn.3922. Epub 2015 Jan 19

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Nature Publishing Group

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