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Curr Opin Rheumatol DOI:10.1097/BOR.0000000000000012

Genome-wide association studies to advance our understanding of critical cell types and pathways in rheumatoid arthritis: recent findings and challenges.

Publication TypeJournal Article
Year of Publication2014
AuthorsDiogo, D, Okada, Y, Plenge, RM
JournalCurr Opin Rheumatol
Date Published2014 Jan
KeywordsArthritis, Rheumatoid, CD4-Positive T-Lymphocytes, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Janus Kinases, Major Histocompatibility Complex, NF-kappa B, Signal Transduction, STAT Transcription Factors

PURPOSE OF REVIEW: A significant number of loci implicated in rheumatoid arthritis (RA) susceptibility have been highlighted by genome-wide association studies (GWAS). Here, we review the recent advances of GWAS in understanding the genetic architecture of RA, and place these findings in the context of RA pathogenesis.

RECENT FINDINGS: Although the interpretation of GWAS findings in the context of the disease biology remains challenging, interesting observations can be highlighted. Integration of GWAS results with cell-type specific gene expression or epigenetic marks have highlighted regulatory T cells and CD4 memory T cells as critical cell types in RA. In addition, many genes in RA loci are involved in the nuclear factor-kappaB signaling pathway or the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. The observation that these pathways are targeted by several approved drugs used to treat the symptoms of RA highlights the promises of human genetics to provide insights in the disease biology, and help identify new therapeutic targets.

SUMMARY: These findings highlight the promises and need of future studies investigating causal genes and underlined mechanisms in GWAS loci to advance our understanding of RA.


Alternate JournalCurr Opin Rheumatol
PubMed ID24276088
Grant ListR01-AR056768 / AR / NIAMS NIH HHS / United States
R01-AR057108 / AR / NIAMS NIH HHS / United States
R01-AR059648 / AR / NIAMS NIH HHS / United States
U01-GM092691 / GM / NIGMS NIH HHS / United States