An international group of investigators has discovered new genes, pathways and cell types that are involved in inherited susceptibility to rheumatoid arthritis (RA). The findings are published online in Nature.
Scientists performed a genome-wide association study (GWAS) meta-analysis in more than 100,000 people of European and Asian descent. They discovered 42 new sites of genetic variation involved in risk for RA. The analysis provides specific locations of genes, DNA sequences or positions on chromosomes for these genetic differences, bringing the catalog of confirmed risk variants for RA to over 100 genetic loci. These findings lead to a better understanding of how new treatments could be developed.
"This study is the culmination of over a decade of work by an extraordinary group of collaborative scientists from around the world," said Peter K. Gregersen, a collaborator on the study, and head of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute for Medical Research www.feinsteininstitute.org. "It provides us with a definitive list of the major common genetic variation involved in this disease, and points the way forward to develop new diagnostic and therapeutic approaches to this illness."
The lead investigator of the study, Robert Plenge, MD, PhD, director of Genetics and Genomics, Division of Rheumatology, Immunology and Allergy at Brigham and Women's Hospital added, "Our study provides a compelling link between human genetics in RA and approved therapies to treat RA. This leads to an intriguing question: can our new genetic discoveries lead to new therapies to treat or cure RA? Further, can a similar approach be used to develop therapies for other complex diseases such as lupus, diabetes and Alzheimer's disease?"
Rheumatoid arthritis is a long-term inflammatory disorder that may affect many tissues and organs, but principally attacks flexible joints. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated. The disease often leads to the destruction of cartilage and fusion of the joints. Rheumatoid arthritis can also produce inflammation in areas of the body including the lungs, membrane around the heart, and white of the eye.
The above story is based on materials provided by North Shore-Long Island Jewish (LIJ) Health System. Note: Materials may be edited for content and length.
- Yukinori Okada, Di Wu, Gosia Trynka, Towfique Raj, Chikashi Terao, Katsunori Ikari, Yuta Kochi, Koichiro Ohmura, Akari Suzuki, Shinji Yoshida, Robert R. Graham, Arun Manoharan, Ward Ortmann, Tushar Bhangale, Joshua C. Denny, Robert J. Carroll, Anne E. Eyler, Jeffrey D. Greenberg, Joel M. Kremer, Dimitrios A. Pappas, Lei Jiang, Jian Yin, Lingying Ye, Ding-Feng Su, Jian Yang, Gang Xie, Ed Keystone, Harm-Jan Westra, Tõnu Esko, Andres Metspalu, Xuezhong Zhou, Namrata Gupta, Daniel Mirel, Eli A. Stahl, Dorothée Diogo, Jing Cui, Katherine Liao, Michael H. Guo, Keiko Myouzen, Takahisa Kawaguchi, Marieke J. H. Coenen, Piet L. C. M. van Riel, Mart A. F. J. van de Laar, Henk-Jan Guchelaar, Tom W. J. Huizinga, Philippe Dieudé, Xavier Mariette, S. Louis Bridges Jr, Alexandra Zhernakova, Rene E. M. Toes, Paul P. Tak, Corinne Miceli-Richard, So-Young Bang, Hye-Soon Lee, Javier Martin, Miguel A. Gonzalez-Gay, Luis Rodriguez-Rodriguez, Solbritt Rantapää-Dahlqvist, Lisbeth Ärlestig, Hyon K. Choi, Yoichiro Kamatani, Pilar Galan, Mark Lathrop, Steve Eyre, John Bowes, Anne Barton, Niek de Vries, Larry W. Moreland, Lindsey A. Criswell, Elizabeth W. Karlson, Atsuo Taniguchi, Ryo Yamada, Michiaki Kubo, Jun S. Liu, Sang-Cheol Bae, Jane Worthington, Leonid Padyukov, Lars Klareskog, Peter K. Gregersen, Soumya Raychaudhuri, Barbara E. Stranger, Philip L. De Jager, Lude Franke, Peter M. Visscher, Matthew A. Brown, Hisashi Yamanaka, Tsuneyo Mimori, Atsushi Takahashi, Huji Xu, Timothy W. Behrens, Katherine A. Siminovitch, Shigeki Momohara, Fumihiko Matsuda, Kazuhiko Yamamoto, Robert M. Plenge. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature, 2013; DOI: 10.1038/nature12873
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