Update on the genetic architecture of rheumatoid arthritis.
Human genetic studies into rheumatoid arthritis (RA) have uncovered more than 100 genetic loci associated with susceptibility to RA and have refined the RA-association model for HLA variants. The majority of RA-risk variants are highly shared across multiple ancestral populations and are located in noncoding elements that might have allele-specific regulatory effects in relevant tissues. Emerging multi-omics data, high-density genotype data and bioinformatic approaches are enabling researchers to use RA-risk variants to identify functionally relevant cell types and biological pathways that are involved in impaired immune processes and disease phenotypes. This Review summarizes reported RA-risk loci and the latest insights from human genetic studies into RA pathogenesis, including how genetic data has helped to identify currently available drugs that could be repurposed for patients with RA and the role of genetics in guiding the development of new drugs.
Department of Biology, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Kwangwoo
K
Kim
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
So-Young
SY
Bang
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
Hye-Soon
HS
Lee
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
Sang-Cheol
SC
Bae
D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D058492:Drug Repositioning; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D010456:Peptides, Cyclic / Q000276:immunology; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics
D001323:Autoantibodies; D006680:HLA Antigens; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide