Genetic studies of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease that results in significant morbidity. As with other complex disorders, genome-wide association studies (GWASs) have greatly contributed to the current understanding of RA etiology. In this review, we describe the genetic configuration of RA as revealed primarily through GWASs and their meta-analyses. In addition, we discuss the pathologic mechanisms of RA as suggested by the findings of genetic and functional studies of individual RA-associated genes, including HLA-DRB1, PADI4, PTPN22, CCR6 and FCRL3, and the potential use of genetic information for RA treatment in clinical practice.

Figure 1.

RA susceptible genes identified by different methodological categories.

Figure 2.

Relative enrichment of RA risk genes in the targets of RA drugs. RA risk genes and the genes in protein-protein interaction (PPI) are significantly enriched in overlap with target genes of approved RA treatment drugs, compared to overlap with target genes of existing drugs for all diseases. Representative connections between RA risk genes and targets of RA treatment drugs are labeled.

Figure 3.

Genetic factors involving rheumatoid arthritis. RA risk genes are presented in italic type. Genes are placed in cells where their functions in the disease pathogenesis are investigated by vitro or in vivo studies. Mϕ: macrophages, Th1: T helper 1 cells, Th17: T helper 17 cells, Treg: regulatory T-cells, ACPA: Anti-cyclic citrullinated peptide antibody.