1. ¹Department of Psychiatry Research, The Zucker Hillside Hospital, Division of the North Shore–Long Island Jewish Health System, Glen Oaks, NY, USA
2. ²The Feinstein Institute for Medical Research, Manhasset, NY, USA
3. ³Department of Psychiatry and Behavioral Science, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA
4. ⁴Harvard Partners Center for Genetics and Genomics, Cambridge, MA, USA
5. ⁵PGxHealth, a Division of Clinical Data, Inc., New Haven, CT, USA
6. ⁶Department of Genetics, Harvard Medical School, Boston, MA, USA

Correspondence: Dr T Lencz, Department of Psychiatry Research, The Zucker Hillside Hospital, 75-59 263rd Street, Glen Oaks, NY 11004, USA. E-mail: lencz@lij.edu

Received 26 January 2007; Revised 2 February 2007; Accepted 4 February 2007; Published online 20 March 2007.

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.