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Meta-Analysis
. 2020 Nov;8(11):e1483.
doi: 10.1002/mgg3.1483. Epub 2020 Sep 23.

The genetic basis for the inverse relationship between rheumatoid arthritis and schizophrenia

Mansour Zamanpoor  1   2 , Hamid Ghaedi  1 , Mir Davood Omrani  1
Affiliations
Meta-Analysis

The genetic basis for the inverse relationship between rheumatoid arthritis and schizophrenia

Mansour Zamanpoor et al. Mol Genet Genomic Med. 2020 Nov.

Abstract

Introduction: Rheumatoid arthritis is a common autoimmune disease and schizophrenia is a relatively common and debilitating neurological disorder. There are several common features between rheumatoid arthritis and schizophrenia. The inverse relationship between rheumatoid arthritis and schizophrenia has been replicated in several studies. Despite evidence for an inverse epidemiological relationship and negative correlations for risk between rheumatoid arthritis and schizophrenia, there are no biological data that directly support this inverse relationship.

Materials and methods': We meta-analyzed the genome-wide association studies to investigate the shared association loci between rheumatoid arthritis and schizophrenia at the genome-wide scale. Rheumatoid arthritis- and schizophrenia-associated loci in most recent genome-wide association studies of rheumatoid arthritis and schizophrenia were tested. Genetic risk score analysis was also conducted to investigate the collective contribution of schizophrenia risk loci to rheumatoid arthritis risk.

Results: Rheumatoid arthritis and schizophrenia meta-genome-wide association study showed a significant peak at the major histocompatibility complex locus on chromosome 6 in both rheumatoid arthritis-schizophrenia meta-genome-wide association study and inverted meta-genome-wide association study datasets. Testing rheumatoid arthritis- and schizophrenia-associated loci outside the human leukocyte antigen region showed no association with both rheumatoid arthritis and schizophrenia at a genome-wide level of significance. Weighted genetic risk scores showed no evidence for a statistically significant association between rheumatoid arthritis and schizophrenia.

Conclusion: The finding of our study is consistent with the role of the major histocompatibility complex locus in the genetic correlation between rheumatoid arthritis and schizophrenia, and suggests that either schizophrenia has an autoimmune basis and/or rheumatoid arthritis has an active neurological component.

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Conflict of interest statement

Authors declare that there is no conflict of interest.

Figures

FIGURE 1
FIGURE 1
QQ plots for meta‐GWAS datasets using METAL. (a) QQ plot for the RA‐schizophrenia meta‐GWAS dataset. (b) QQ plot for the inverted meta‐GWAS analysis of RA and schizophrenia. Deviations from the diagonal line were observed in both RA‐schizophrenia meta‐GWAS dataset.
FIGURE 2
FIGURE 2
Manhattan plot of ‐log10 (p value) in the combined RA‐schizophrenia meta‐GWAS dataset. There was a significant peak on chromosome 6. Data are colored as gray and blue according to chromosome and base‐pair position.
FIGURE 3
FIGURE 3
Manhattan plot of ‐log10 (p value) in the inverted meta‐GWAS of RA and schizophrenia. There was a significant peak on chromosome 6. Data are colored as gray and blue according to chromosome.
FIGURE 4
FIGURE 4
LocusZoom plot showing the most significant associated region within the MHC region on chromes 6 in RA‐schizophrenia meta‐GWAS dataset.
FIGURE 5
FIGURE 5
LocusZoom plot showing the most significant associated region within the MHC region on chromes 6 in RA‐schizophrenia inverted meta‐GWAS dataset.
FIGURE 6
FIGURE 6
Schizophrenia genetic risk scores explaining variance in RA status in an independent test cohort. Scores are calculated across cutoff thresholds (PT).
FIGURE 7
FIGURE 7
RA genetic risk scores explaining variance in schizophrenia status in an independent test cohort. Scores are calculated across cutoff thresholds (PT).
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References

    1. Altamura, A. C. , Buoli, M. , & Pozzoli, S. (2020). Role of immunological factors in the pathophysiology and diagnosis of bipolar disorder: comparison with schizophrenia. Psychiatry Clin Neurosci, 68, 21–36. - PubMed
    1. Allebeck, P. , Rodvall, Y. , & Wistedt, B. (1985). Incidence of rheumatoid arthritis among patients with schizophrenia, affective psychosis and neurosis. Acta Psychiatrica Scandinavica, 71, 615–619. - PubMed
    1. Baldwin, J. A. (1980). Schizophrenia and physical disease: a preliminary analysis of the data from the Oxford Record Linkage Study In Lancaster H. G. (Ed.), The Biochemistry of Schizophrenia and Addiction. Search of a Common Factor, (pp. 297‐318). Dordrecht, the Netherlands: MTP.
    1. Benros, M. E. , Pedersen, M. G. , Rasmussen, H. , Eaton, W. W. , Nordentoft, M. , & Mortensen, P. B. (2014). A nationwide study on the risk of autoimmune diseases in individuals with a personal or a family history of schizophrenia and related psychosis. American Journal of Psychiatry, 171(2), 218–226. 10.1176/appi.ajp.2013.13010086 - DOI - PubMed
    1. Chen, S.‐J. , Chao, Y.‐L. , Chen, C.‐Y. , Chang, C.‐M. , Wu, E.‐H. , Wu, C.‐S. , … Tsai, H.‐J. (2012). Prevalence of autoimmune diseases in in‐patients with schizophrenia: nationwide population‐based study. The British Journal of Psychiatry, 200(5), 374–380. - PubMed

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