The genetic basis for the inverse relationship between rheumatoid arthritis and schizophrenia. 2020

Mansour Zamanpoor, and Hamid Ghaedi, and Mir Davood Omrani
Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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. 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. 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. 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.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001172 Arthritis, Rheumatoid A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. Rheumatoid Arthritis
D012559 Schizophrenia A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior. Dementia Praecox,Schizophrenic Disorders,Disorder, Schizophrenic,Disorders, Schizophrenic,Schizophrenias,Schizophrenic Disorder
D056426 Genetic Loci Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE. Genetic Locus,Loci, Genetic,Locus, Genetic
D020641 Polymorphism, Single Nucleotide A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population. SNPs,Single Nucleotide Polymorphism,Nucleotide Polymorphism, Single,Nucleotide Polymorphisms, Single,Polymorphisms, Single Nucleotide,Single Nucleotide Polymorphisms

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