Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Mol Genet Genomic Med. 2020 Nov;8(11):e1483. doi: 10.1002/mgg3.1483. Epub 2020 Sep 23.
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.
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.
类风湿性关节炎是一种常见的自身免疫性疾病，精神分裂症是一种相对常见且使人虚弱的神经疾病。类风湿性关节炎和精神分裂症之间有几个共同的特征。几项研究复制了类风湿性关节炎和精神分裂症之间的反比关系。尽管有证据表明类风湿性关节炎和精神分裂症之间存在流行病学的反比关系和风险的负相关，但没有生物学数据直接支持这种反比关系。
我们对全基因组关联研究进行了荟萃分析，以在全基因组范围内研究类风湿性关节炎和精神分裂症之间共同的关联位点。测试了最近的类风湿性关节炎和精神分裂症全基因组关联研究中与类风湿性关节炎和精神分裂症相关的位点。还进行了遗传风险评分分析，以研究精神分裂症风险位点对类风湿性关节炎风险的集体贡献。
类风湿性关节炎和精神分裂症全基因组关联研究在类风湿性关节炎-精神分裂症全基因组关联研究和反转全基因组关联研究数据集中均在 6 号染色体主要组织相容性复合物位点显示出显著的峰。在人类白细胞抗原区域之外测试与类风湿性关节炎和精神分裂症相关的位点，在全基因组水平上与类风湿性关节炎和精神分裂症均无关联。加权遗传风险评分显示，类风湿性关节炎和精神分裂症之间没有统计学上显著的关联。
我们研究的发现与主要组织相容性复合物位点在类风湿性关节炎和精神分裂症遗传相关性中的作用一致，这表明精神分裂症具有自身免疫基础，或者类风湿性关节炎具有活跃的神经成分。
