Genomic and trans-omics analysis and precision medicine of rheumatoid arthritis

Abstract

  With the recent increase in the scale of human genome research and the development of genetic statistical methods, much progress has been made in the genome analysis of rheumatoid arthritis. Genome-wide association studies（GWASs）of rheumatoid arthritis have previously reported that more than 100 loci were significantly associated with the risk of rheumatoid arthritis. Because most of the disease-sensitive SNPs identified by GWAS are located in non-coding regions, it is often difficult to interpret their biological significance. Our group demonstrated trans-omics analysis by integrating the results of GWASs and epigenetic data, which clarified certain inflammatory cell types that were significantly associated with the risk of rheumatoid arthritis. It has been also known that in rheumatoid arthritis, the human microbiome was involved in the etiology and progression of the rheumatoid arthritis. Our group demonstrated metagenome-wide association analysis（MWAS）of the gut microbiome by using whole-genome shotgun sequencing and found association among the human genome, the gut microbiome, and rheumatoid arthritis. Furthermore, in recent years, the application to personalized medicine by using human genomics is attracting attention. Polygenic risk score（PRS）predicts disease risk based on SNPs identified by GWAS. Our group analyzed the data of international biobanks of approximately 670,000 participants and identified the biomarker associated with human lifespan.