Genomewide association for schizophrenia in the CATIE study: results of stage 1

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.

Genome-wide association study of recurrent major depressive disorder in two European case–control cohorts

“…56 These GWAS clearly indicated that sample size in the order of several thousands are required to provide sufficient statistical power to detect SNPs with such small effect. 57 This is likely to be the case also for psychiatric disorders, as suggested by initial GWAS efforts for schizophrenia and BD [51][52][53][54][58][59][60][61] and by our work, which represents the first GWAS to be reported for recurrent MDD. The sample size used in our study was clearly not powered enough to detect SNP with small effects.…”

Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses

“…Future studies need to address the effect of heterozygosity, or the carriage of one or two reduced function alleles on the predisposition to the response to antipsychotics efficacy and toxicity). Interestingly, genome-wide association studies of patients enrolled in the CATIE trial of antipsychotic medications 112 has recently failed to find an association between CYP2D6 and schizophrenia, 113 and between CYP2D6 (or indeed any other genetic marker or haplotype association) and TD. 114 This further highlights the complexity of schizophrenia and its treatments and the need to have well-powered studies to disentangle the factors predisposing to the disease from those predisposing to variability in drug response.…”

ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schizophrenia

“…Despite being relatively under-powered to replicate such a modest effect, two of three recently reported large SZ GWAS studies (Purcell et al, 2009;Sullivan et al, 2008) and a discrete replication study by Riley et al (2009) supported association between the same risk allele and increased SZ risk. Copy number variation at this locus has also been identified for psychosis (Steinberg et al, 2010).…”