Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
By C. O’Dushlaine, L. Rossin, Phil H. Lee, L. Duncan, Neelroop Parikshak, S. Newhouse, S. Ripke, Benjamin M. Neale, Shaun Purcell, Danielle Posthuma and 365 more. Nature Neuroscience, 2015
750 citations recorded by the source corpus.
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.
Subfields: Biological Psychiatry, Genetics
View Paper: https://www.semanticscholar.org/paper/aa57f6775b7c1ec25b4a7703a187d7d426e2c166
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In Genetics
Citations in the corpus
- Genetic identification of brain cell types underlying schizophrenia (2017, methodology): “We evaluated the effect of different choices of bin size including 35 kb upstream – 10 kb downstream (as often used by the PGC 48 ), 150 kb upstream – 10 kb downstream, and 150 kb upstream – 150 kb downstream (GTEx 21 Supplemental Figure 9 from).”