Association of Schizophrenia and Autoimmune Diseases: Linkage of Danish National Registers

Eaton, William W.; Byrne, Majella; Ewald, Henrik; Mors, Ole; Chen, Chuan Yu; Agerbo, Esben; Mortensen, Preben Bo

doi:10.1176/appi.ajp.163.3.521

Cited by 475 publications

(369 citation statements)

References 74 publications

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“…33,34 Similarly, an elevated level of GM-CSF in synovial fluid has been implicated in the inflammatory pathophysiology of rheumatoid arthritis (RA), 35 and SCZ patients have consistently demonstrated a reduced prevalence of RA. 36 Moreover, SCZ patients show increased incidence of other inflammatory autoimmune disorders such as celiac disease and Sjö gren's syndrome before SCZ onset, and prevalence of many autoimmune disorders is increased in parents of SCZ patients. 36 These patterns of comorbidity, both in patients and first-degree relatives, might also be explained by gene-environment interactions of abnormal cytokine receptor genes and varying levels of environmental exposures.…”

Section: Discussionmentioning

confidence: 99%

“…36 Moreover, SCZ patients show increased incidence of other inflammatory autoimmune disorders such as celiac disease and Sjö gren's syndrome before SCZ onset, and prevalence of many autoimmune disorders is increased in parents of SCZ patients. 36 These patterns of comorbidity, both in patients and first-degree relatives, might also be explained by gene-environment interactions of abnormal cytokine receptor genes and varying levels of environmental exposures.…”

Section: Discussionmentioning

confidence: 99%

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Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia

et al. 2007

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Schizophrenia is a strongly heritable disorder, and identification of potential candidate genes has accelerated in recent years. Genomewide scans have identified multiple large linkage regions across the genome, with fine-mapping studies and other investigations of biologically plausible targets demonstrating several promising candidate genes of modest effect. The recent introduction of technological platforms for whole-genome association (WGA) studies can provide an opportunity to rapidly identify novel targets, although no WGA studies have been reported in the psychiatric literature to date. We report results of a case-control WGA study in schizophrenia, examining B500 000 markers, which revealed a strong effect (P = 3.7 Â 10 À7 ) of a novel locus (rs4129148) near the CSF2RA (colony stimulating factor, receptor 2 alpha) gene in the pseudoautosomal region. Sequencing of CSF2RA and its neighbor, IL3RA (interleukin 3 receptor alpha) in an independent case-control cohort revealed both common intronic haplotypes and several novel, rare missense variants associated with schizophrenia. The presence of cytokine receptor abnormalities in schizophrenia may help explain prior epidemiologic data relating the risk for this illness to altered rates of autoimmune disorders, prenatal infection and familial leukemia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia

et al. 2007

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“…Inflammation is suggested to be an inherent part of schizophrenia. Reports show that schizophrenia patients have either higher or lower prevalence of some autoimmune disorders than expected 38 and that the efficacy of anti-inflammatory drugs differs in patients. 39 The latter observations could support the viral hypothesis of schizophrenia.…”

Section: 2e-02mentioning

confidence: 99%

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

et al. 2012

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and The PGC Schizophrenia (GWAS) Consortium 7There is genetic evidence that schizophrenia is a polygenic disorder with a large number of loci of small effect on disease susceptibility. Genome-wide association studies (GWASs) of schizophrenia have had limited success, with the best finding at the MHC locus at chromosome 6p. A recent effort of the Psychiatric GWAS consortium (PGC) yielded five novel loci for schizophrenia. In this study, we aim to highlight additional schizophrenia susceptibility loci from the PGC study by combining the top association findings from the discovery stage (9394 schizophrenia cases and 12 462 controls) with expression QTLs (eQTLs) and differential gene expression in whole blood of schizophrenia patients and controls. We examined the 6192 singlenucleotide polymorphisms (SNPs) with significance threshold at Po0.001. eQTLs were calculated for these SNPs in a sample of healthy controls (n¼437). The transcripts significantly regulated by the top SNPs from the GWAS meta-analysis were subsequently tested for differential expression in an independent set of schizophrenia cases and controls (n¼202). After correction for multiple testing, the eQTL analysis yielded 40 significant cis-acting effects of the SNPs. Seven of these transcripts show differential expression between cases and controls. Of these, the effect of three genes (RNF5, TRIM26 and HLA-DRB3) coincided with the direction expected from meta-analysis findings and were all located within the MHC region. Our results identify new genes of interest and highlight again the involvement of the MHC region in schizophrenia susceptibility.

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“…Similarly to other autoimmune disorders, RA is a disease of multifactorial etiology. The genetic predisposition is responsible for approximately 60% of the whole disease risk, while environmental factors, such as infections by microbial agents [16] , smoking [17,18] , obesity, or schizophrenia of first-degree relatives [19,20] , and abnormalities of the autoimmune processes also play a role. The association with the human leukocyte antigen (HLA)-DRB1 locus was the first to be described to confer risk for RA (50% of the overall genetic predisposition) [21] .…”

Section: Topic Highlightmentioning

confidence: 99%

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

Magyari

Várszegi

Kövesdi

et al. 2014

WJO

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Rheumatoid arthritis (RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologic targets for RA treatment. The identification of diseaseassociated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual's genetics.

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Association of Schizophrenia and Autoimmune Diseases: Linkage of Danish National Registers

Abstract: Schizophrenia is associated with a larger range of autoimmune diseases than heretofore suspected. Future research on comorbidity has the potential to advance understanding of pathogenesis of both psychiatric and autoimmune disorders.

Cited by 475 publications

References 74 publications

Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia

Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

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