It has consistently been reported that patients with schizophrenia have an increased risk of type-2 diabetes. To investigate a genetic link between these two diseases, the combined effects of the PLA2G4A, PTGS2 and PPARG genes were tested among 221 British nuclear families consisting of fathers, mothers and affected offspring with schizophrenia. A total of 10 single nucleotide polymorphisms (SNPs) were tested and the likelihood-based association analysis for nuclear families was used to analyse the genotyping data. Eight SNPs detected across the PPARG gene did not show allelic association with schizophrenia; a weak association was detected at rs2745557 in the PTGS2 locus (chi2=4.19, p=0.041) and rs10798059 in the PLA2G4A locus (chi2=4.28, p=0.039) but these associations did not survive after 10,000 permutations to correct the p-value (global p=0.246). The gene-gene interaction test did not show any evidence of either cis-phase interactions for the PLA2G4A and PTGS2 combinations or a trans-phase interaction for the PLA2G4A and PPARG combinations. The PPARG gene has been reported to be strongly associated with type-2 diabetes, but the present study did not support the hypothesis that the PPARG gene may also play an important role in the development of schizophrenia.