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Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia

Molecular Psychiatry volume 12, pages 572–580 (2007)Cite this article

Abstract

Schizophrenia is a strongly heritable disorder, and identification of potential candidate genes has accelerated in recent years. Genomewide scans have identified multiple large linkage regions across the genome, with fine-mapping studies and other investigations of biologically plausible targets demonstrating several promising candidate genes of modest effect. The recent introduction of technological platforms for whole-genome association (WGA) studies can provide an opportunity to rapidly identify novel targets, although no WGA studies have been reported in the psychiatric literature to date. We report results of a case–control WGA study in schizophrenia, examining ∼500 000 markers, which revealed a strong effect (P=3.7 × 10−7) of a novel locus (rs4129148) near the CSF2RA (colony stimulating factor, receptor 2 alpha) gene in the pseudoautosomal region. Sequencing of CSF2RA and its neighbor, IL3RA (interleukin 3 receptor alpha) in an independent case–control cohort revealed both common intronic haplotypes and several novel, rare missense variants associated with schizophrenia. The presence of cytokine receptor abnormalities in schizophrenia may help explain prior epidemiologic data relating the risk for this illness to altered rates of autoimmune disorders, prenatal infection and familial leukemia.

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Acknowledgements

This work was supported by the Donald and Barbara Zucker Foundation, internal funding from the North Shore – Long Island Jewish Health System, Clinical Data, Inc., a Keyspan Fellowship Award (TL) and grants from the Stanley Foundation (AKM), the National Alliance for Research on Schizophrenia and Depression (AKM), and the NIH (MH065580 to TL; MH074543 to JMK; MH001760 to AKM). We thank Christophe Lambert and Josh Forsythe of Golden Helix, Inc., for their computing expertise and technical support.

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Authors and Affiliations

  1. Department of Psychiatry Research, Division of the North Shore–Long Island Jewish Health System, The Zucker Hillside Hospital, Glen Oaks, NY, USA

    T Lencz, J M Kane & A K Malhotra

  2. The Feinstein Institute for Medical Research, Manhasset, NY, USA

    T Lencz, J M Kane & A K Malhotra

  3. Department of Psychiatry and Behavioral Science, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA

    T Lencz, J M Kane & A K Malhotra

  4. Harvard Partners Center for Genetics and Genomics, Cambridge, MA, USA

    T V Morgan & R Kucherlapati

  5. a Division of Clinical Data, PGxHealth, Inc., New Haven, CT, USA

    M Athanasiou, B Dain & C R Reed

  6. Department of Genetics, Harvard Medical School, Boston, MA, USA

    R Kucherlapati

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  1. T Lencz
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Correspondence to T Lencz.

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Lencz, T., Morgan, T., Athanasiou, M. et al. Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Mol Psychiatry 12, 572–580 (2007). https://doi.org/10.1038/sj.mp.4001983

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