1. ¹Departments of Genetics, Psychiatry, and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
2. ²Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
3. ³Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
4. ⁴Department of Statistics, North Carolina State University, Raleigh, NC, USA
5. ⁵Department of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA
6. ⁶Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
7. ⁷School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
8. ⁸Department of Statistics, Eli Lilly and Company, Indianapolis, IN, USA
9. ⁹Department of Experimental Medicine, Eli Lilly and Company, Indianapolis, IN, USA
10. ¹⁰Department of Psychiatry, Columbia University, New York, NY, USA

Correspondence: Professor Dr PF Sullivan, Department of Genetics, University of North Carolina, CB no. 7264, 4109D, Neurosciences Research Building, Chapel Hill, NC 27599-7264, USA. E-mail: pfsulliv@med.unc.edu; Dr SL Close, Department of Experimental Medicine, Eli Lilly and Company, Indianapolis, IN 46285, USA. E-mail: kirkwood_sandra@lilly.com

Received 23 October 2007; Revised 7 January 2008; Accepted 11 January 2008; Published online 18 March 2008.

Abstract

Little is known for certain about the genetics of schizophrenia. The advent of genomewide association has been widely anticipated as a promising means to identify reproducible DNA sequence variation associated with this important and debilitating disorder. A total of 738 cases with DSM-IV schizophrenia (all participants in the CATIE study) and 733 group-matched controls were genotyped for 492 900 single-nucleotide polymorphisms (SNPs) using the Affymetrix 500K two-chip genotyping platform plus a custom 164K fill-in chip. Following multiple quality control steps for both subjects and SNPs, logistic regression analyses were used to assess the evidence for association of all SNPs with schizophrenia. We identified a number of promising SNPs for follow-up studies, although no SNP or multimarker combination of SNPs achieved genomewide statistical significance. Although a few signals coincided with genomic regions previously implicated in schizophrenia, chance could not be excluded. These data do not provide evidence for the involvement of any genomic region with schizophrenia detectable with moderate sample size. However, a planned genomewide association study for response phenotypes and inclusion of individual phenotype and genotype data from this study in meta-analyses hold promise for eventual identification of susceptibility and protective variants.