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

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  1. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Genome-wide association study implicates CHRNA2 in cannabis use disorder

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  3. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept

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  4. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

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  5. PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Clinical association to FKBP5 rs1360780 in patients with depression

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A large-scale genomic investigation of susceptibility to infection and its association with mental disorders in the Danish population

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  4. Genetic risk scores for major psychiatric disorders and the risk of postpartum psychiatric disorders

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  • The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium
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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.

Original languageEnglish
JournalNature Neuroscience
ISSN1097-6256
DOIs
Publication statusPublished - 19 Jan 2015

ID: 44854524