Biological insights from 108 schizophrenia-associated genetic loci

Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T. R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune Hannes Pers, Esben Agerbo, Ditte Demontis, Thomas Hansen, Mads Vilhelm Hollegaard, David M. Hougaard, Ole Mors, Thomas Werge

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been
    previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, andare consistent with leadingpathophysiologicalhypotheses. Independentof genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
    Original languageEnglish
    JournalNature
    Volume511
    Pages (from-to)421-427
    ISSN0028-0836
    DOIs
    Publication statusPublished - 2014

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