HLA Antigens and Schizophrenia

Crowe, Raymond R.; Thompson, John S.; Flink, Ronald J.; Weinberger, Bernice

doi:10.1001/archpsyc.1979.01780020121014

Cited by 35 publications

(7 citation statements)

References 8 publications

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“…At least 7 studies have shown HLA-A9 to be elevated in patients with paranoid schizophrenia (31). Studies that divided HLA-A9 into subspecies found associations between schizophrenia and both HLA-A23 (32) and HLA-A24 (33). However, Alexander and colleagues found no association between either HLA-A23 or A24 and the paranoid subtype and expressed doubt about an association between HLA-A24 and schizophrenia (34).…”

Section: Discussionmentioning

confidence: 99%

Genetic Associations between Delusional Disorder and Paranoid Schizophrenia: A Novel Etiologic Approach

et al. 2006

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Objectives: Genetic associations between delusional disorder and paranoid schizophrenia are not well understood, although involvement of biological factors has been suspected. We investigated the incidence of human leukocyte antigen (HLA) class I alleles in patients with delusional disorder and paranoid schizophrenia, first, to explore a possible immunogenetic etiology of these paranoid disorders and, second, to determine whether they share similar etiologic mechanisms. Method:We employed a nested case-control study design. Psychiatric reference data were available for 38 500 patients attending a hospital-based psychiatric outpatient department between 1998 and 2005. We enrolled 100 patients with delusional disorder and 50 patients with paranoid schizophrenia as the subject cases, using DSM-IV criteria. We considered equivalent numbers of healthy volunteers matched for age and ethnic background as control subjects. All subjects came from an India-born Bengali population. We applied the polymerase chain reaction-based molecular typing method to all patients and healthy subjects. Results:The HLA-A*03 gene is significantly associated with delusional disorder as well as with paranoid schizophrenia. This HLA gene alone or in linkage disequilibrium with other HLA genes or other closely linked non-HLA genes may influence susceptibility to delusional disorder and paranoid schizophrenia. Conclusions:The study reveals important associations between HLA genes and paranoid disorders. Delusional disorder and paranoid schizophrenia may share similar etiologic mechanisms. This preliminary observation may help our understanding of the genetic basis of these paranoid disorders. Clinical Implications· This preliminary study may help us to understand the genetic basis of delusional disorder and paranoid schizophrenia. · This investigation may further help in understanding whether delusional disorder and paranoid schizophrenia bear similar etiologic mechanisms based on HLA associations. · The study may strengthen our knowledge of the paranoid spectrum concept. Limitations· The sample size was small, and the study needs to be replicated in a large sample. · We studied the distribution of HLAs in delusional disorder as a whole, rather than by subtype. · We did not study the familial clustering pattern of these HLA genes.

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Section: Discussionmentioning

confidence: 99%

Genetic Associations between Delusional Disorder and Paranoid Schizophrenia: A Novel Etiologic Approach

et al. 2006

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“…Others have reported common sequence variants of very small effect, including several in the human leukocyte antigen (HLA) region (6p) 130–137. The latter findings recall early studies of protein-based HLA polymorphisms 138,139. Meta-analysis using GWAS data from thousands of individuals with schizophrenia has revealed a few weak-effect associations, in the ZNF804A gene 140–143.…”

Section: Schizophrenia In the Molecular Agementioning

confidence: 76%

Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era

Costain¹,

Bassett²

2012

TACG

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Schizophrenia is a complex neuropsychiatric disease with documented clinical and genetic heterogeneity, and evidence for neurodevelopmental origins. Driven by new genetic technologies and advances in molecular medicine, there has recently been concrete progress in understanding some of the specific genetic causes of this serious psychiatric illness. In particular, several large rare structural variants have been convincingly associated with schizophrenia, in targeted studies over two decades with respect to 22q11.2 microdeletions, and more recently in large-scale, genome-wide case-control studies. These advances promise to help many families afflicted with this disease. In this review, we critically appraise recent developments in the field of schizophrenia genetics through the lens of immediate clinical applicability. Much work remains in translating the recent surge of genetic research discoveries into the clinic. The epidemiology and basic genetic parameters (such as penetrance and expression) of most genomic disorders associated with schizophrenia are not yet well characterized. To date, 22q11.2 deletion syndrome is the only established genetic subtype of schizophrenia of proven clinical relevance. We use this well-established association as a model to chart the pathway for translating emerging genetic discoveries into clinical practice. We also propose new directions for research involving general genetic risk prediction and counseling in schizophrenia.

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“…Up until the 1980s, many studies used unspecified clinical diagnoses [Ivanyi et al, 1976;Asaka et al, 1981]. Where specified, a variety of criteria were used including Bleuler's definition [Eberhard et al, 1975], Feighner criteria [Crowe et al, 1979], Research Diagnostic Criteria [Luchins et al, 1980], Manual of the International Classification of Diseases, Injuries, and Causes of Death (ICD) 9, [Mc-Guffin et al, 1978], and more recently Diagnostic and Statistical Manual of Mental Disorders (DSM) III [Sasaki et al, 1994], DSM-III-R [Blackwood et al, 1996], and ICD 10 [Nimgaonkar et al, 1995]. In addition to this possible variation in the schizophrenia phe- notype, the disease was subtyped in a number of different ways, including the criteria of Tsuang and Winokur [1974] and individual study criteria [Smeraldi et al, 1976].…”

Section: Diagnostic Methodsmentioning

confidence: 99%

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

Hawi¹,

Gibson²,

Straub³

et al. 1999

Am. J. Med. Genet.

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Susceptibility to autoimmunity is strongly influence by genes clustered in the MHC region, particularly class I and class II antigens. It has been proposed that there is an immune component in the aetiology of schizophrenia, and the distribution of human leukocyte antigens (HLA) in schizophrenic patients and controls 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-DQbeta*0602. Small sample size, variable diagnostic methodology, unreliable laboratory and statistical procedures, and possible mismatching of cases and controls may have contributed to a lack of consistency of results to date. Therefore, in this investigation we used a large and carefully diagnosed homogeneous Irish familial schizophrenic sample compared with ethnically matched controls. All alleles were determined using polymerase chain reaction amplification followed by short specific oligoprobes. We found no evidence of association with 80 HLA alleles (some previously not examined) from 4 genes. Our data therefore do not support the involvement of these classical HLA loci in the aetiology of schizophrenia at least in these Irish families. The remaining classical HLA loci (HLA-B and HLA-C) should be typed when reliable DNA-based methods become available.

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HLA Antigens and Schizophrenia

Cited by 35 publications

References 8 publications

Genetic Associations between Delusional Disorder and Paranoid Schizophrenia: A Novel Etiologic Approach

Genetic Associations between Delusional Disorder and Paranoid Schizophrenia: A Novel Etiologic Approach

Clinical applications of schizophrenia genetics: genetic diagnosis, risk, and counseling in the molecular era

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

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