1. ¹Department of Psychiatry, Harvard Medical School, and Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Charlestown, MA, USA
2. ²Broad Institute, Cambridge, MA, USA
3. ³Veterans Administration, Syracuse, NY, USA
4. ⁴Center for Psychiatric and Molecular Genetics, SUNY/Upstate Medical University, Syracuse, NY, USA
5. ⁵Psicologia Medica, Universidade de Coimbra, Coimbra, Portugal
6. ⁶Psychiatry Service, Ponta Delgada, Azores, Portugal
7. ⁷McGill University and Genome Quebec Innovation Centre, Montreal, Canada H3A 1A4
8. ⁸Clarke Division, Centre for Addiction and Mental Health Toronto, CA, USA

Correspondence: Dr P Sklar, Psychiatric and Neurodevelopmental Genetics Unit, 149 13th Street, Charlestown, MA 02129, USA. E-mail: sklar@psych.mgh.harvard.edu

Received 9 June 2003; Revised 21 July 2003; Accepted 21 July 2003; Published online 30 December 2003.

Abstract

Schizophrenia is a common psychiatric disorder with a complex genetic etiology. To understand the genetic basis of this syndrome in Portuguese Island populations, we performed a genome-wide scan of 29 families with schizophrenia, which identified a single region on 5q31–5q35 with strong linkage (NPL=3.09, P=0.0012 at D5S820). Empirical simulations set a genome-wide threshold of NPL=3.10 for significant linkage. Additional support for this locus in schizophrenia comes from higher-density mapping and mapping of 11 additional families. The combined set of 40 families had a peak NPL=3.28 (P=0.00066) at markers D5S2112–D5S820. These data and previous linkage findings from other investigators provide strong and consistent evidence for this genomic region as a susceptibility locus for schizophrenia. Exploratory analyses of a novel phenotype, psychosis, in families with schizophrenia and bipolar disorder detected evidence for linkage to the same markers as found in schizophrenia (peak NPL=3.03, P=0.0012 at D5S820), suggesting that this locus may be responsible for the psychotic symptoms observed in both diseases.