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

TY - JOUR

T1 - Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

AU - Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium

AU - Kuntsi, Jonna Pauliina

AU - Breen, Gerome Daniel

AU - Lewis, Cathryn

AU - Asherson, Philip

AU - Young, Allan

AU - Sonuga-Barke, Edmund

PY - 2015/2

Y1 - 2015/2

N2 - 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.

AB - 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.

KW - Brain

KW - Databases, Genetic

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Histones

KW - Humans

KW - Mental Disorders

KW - Signal Transduction

U2 - 10.1038/nn.3922

DO - 10.1038/nn.3922

M3 - Article

C2 - 25599223

SN - 1097-6256

VL - 18

SP - 199

EP - 209

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 2

ER -