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Schizophrenia and HLA: a review.
P Wright1, V L Nimgaonkar, P T Donaldson
1Department of Psychological Medicine, Institute of Psychiatry and King's College Hospital, De Crespigny Park, London SE5 8AF, UK.
Schizophrenia Research
|February 13, 2001
Summary
Genetic studies suggest a weak link between human leucocyte antigens (HLA) and schizophrenia susceptibility. While some HLA alleles show associations, robust evidence remains inconclusive, necessitating refined research methodologies for clarity.
Area of Science:
- Immunogenetics
- Psychiatric Genetics
Background:
- Numerous studies have investigated the genetic association between human leucocyte antigens (HLA) and schizophrenia.
- Linkage studies have also suggested a schizophrenia susceptibility locus on chromosome 6p, near the HLA region.
Purpose of the Study:
- To review and critically evaluate published investigations of HLA association with schizophrenia from 1974 to date.
- To briefly review chromosome 6p linkage studies relevant to schizophrenia.
Main Methods:
- Comprehensive literature review of HLA association studies in schizophrenia.
- Review of linkage studies on chromosome 6p for schizophrenia susceptibility loci.
Main Results:
- Several HLA antigens/alleles (A9/A24, A28, A10, DRB1*01, DRw6) have been reported in association with schizophrenia, but results may be subject to Type I errors.
- Hypothesis-driven negative associations were reported for DRB1*04 and DQB1*0602.
- Overall, HLA association studies provide weak evidence for schizophrenia loci near the HLA region; recent studies controlling for confounders found no association.
- Linkage studies suggest a potential locus within the HLA region, but evidence is not conclusive.
Conclusions:
- Current HLA association investigations provide limited evidence for schizophrenia susceptibility loci near the HLA region.
- Linkage studies offer some support for a locus in the HLA region, but findings are inconclusive.
- Future research should utilize stringent methodologies, including operational diagnostic criteria, screened subjects, HLA genotyping, and advanced statistical analyses like transmission disequilibrium and haplotype relative risk studies.