Schizophrenia and HLA: No association with PCR-SSOP typed classical loci in a large Irish familial sample

Susceptibility to autoimmunity is strongly influenced by genes clustered in the MHC region, particularly Class I and Class II antigens. The distribution of HLA antigens in schizophrenic patients has been investigated in numerous studies. Positive associations have been reported between schizophrenia and the HLA-A1, A2, A9, B5, Cw4, and DR8 and negative associations with HLA-DR4 and HLA-DQβ*0602. In this investigation, we have used a large and carefully diagnosed homogeneous Irish familial schizophrenic sample compared to ethnically matched controls and found no evidence of any of the reported associations with 86 HLA alleles (some previously not examined). All alleles were determined using polymerase chain reaction amplification followed by probing with short specific oligoprobes. Our data do not support the involvement of these classical HLA alleles in the aetiology of schizophrenia. Previous studies are likely to represent false positive findings which can be attributed to a combination of factors.