Genetic association study of the P300 endophenotype in schizophrenia

Objective: Although reduced amplitude of the P300 event-related potential is a well-documented intermediate phenotype of schizophrenia, little is known about its genetic underpinnings in patients with schizophrenia. This study aims to examine associations between P300 and a range of candidate genetic variants, selected from either candidate gene studies or genome-wide association studies, in a large sample of patients with schizophrenia. Methods: P300 amplitude at the midline parietal electrode and 193 single nucleotide polymorphisms (SNPs) in 67 genes were assessed in 336 patients with schizophrenia. The association between each SNP and P300 amplitude, controlled for illness duration and gender, was evaluated. Associations at p<.01 were considered of potential relevance, while Bonferroni correction was applied to determine formal statistical significance (Bonferroni-corrected threshold of significance p=.0003). Results: Of the 193 selected SNPs, 4 SNPs showed potentially relevant association with P300 amplitude at a significance level of p<.01. One of these SNPs, rs1045642 in ABCB1, was most convincingly associated with P300 amplitude, reaching formal (Bonferroni-corrected) significance, while there was evidence for possible association with rs1572899 in DISC-1, rs6265 in BDNF and rs1625579 in MIR137. Conclusion: Genetic variation in ABCB1 may be associated with P300 amplitude in patients with schizophrenia. This result may encourage further efforts to elucidate the genetic underpinnings of P300 generation. (C) 2012 Elsevier B.V. All rights reserved.