Journal
NATURE NEUROSCIENCE
Volume 18, Issue 2, Pages 199-209Publisher
NATURE PORTFOLIO
DOI: 10.1038/nn.3922
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Funding
- National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London
- Maudsley NHS Foundation Trust
- King's College London
- US National Institute of Mental Health (NIMH) [K99MH101367]
- NIMH [U01 MH085520]
- Netherlands Scientific Organization (NOW) [480-05-003]
- Dutch Brain Foundation
- VU University
- MRC [G0800509, G0300189, G1000708] Funding Source: UKRI
- Lundbeck Foundation [R155-2014-1724] Funding Source: researchfish
- Medical Research Council [MR/L010305/1, G9817803B, G0300189, G0800509] Funding Source: researchfish
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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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