Relationship of HLA to schizophrenia in 10 nuclear families

We tested the hypothesis of linkage of HLA (human leukocyte antigens) and schizophrenia in 10 nuclear families that were ascertained on the basis of at least two siblings affected with chronic schizophrenia (SCH), as defined by Research Diagnostic Criteria, with or without superimposed affective disorder. All available parents and siblings were interviewed and typed for HLA antigens at the A, B, C, and Dr loci. Lod scores for linkage between HLA and a putative SCH-locus were calculated using the program LIPED, assuming several possible models for the mode of transmission of the SCH locus. Linkage was also tested with DSM-III schizotypal and paranoid personality disorders considered as part of the illness phenotype. The lod score analysis indicated that for most models of inheritance of schizophrenia, close linkage to HLA could be excluded. The results did not change if individuals with "spectrum" disorders were considered affected. We also tested for linkage using the affected sib-pair method which does not require any assumptions about the mode of transmission of the illness. The results of this analysis also indicated that linkage to HLA was very unlikely. If our results are considered together with other published studies, a susceptibility locus for schizophrenia or "schizophrenia spectrum" is not likely to be in the HLA region of chromosome 6.