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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- Okada, Yukinori (author)
- Wu, Di (author)
- Trynka, Gosia (author)
- show more...
- Raj, Towfique (author)
- Terao, Chikashi (author)
- Ikari, Katsunori (author)
- Kochi, Yuta (author)
- Ohmura, Koichiro (author)
- Suzuki, Akari (author)
- Yoshida, Shinji (author)
- Graham, Robert R (author)
- Manoharan, Arun (author)
- Ortmann, Ward (author)
- Bhangale, Tushar (author)
- Denny, Joshua C (author)
- Carroll, Robert J (author)
- Eyler, Anne E (author)
- Greenberg, Jeffrey D (author)
- Kremer, Joel M (author)
- Pappas, Dimitrios A (author)
- Jiang, Lei (author)
- Yin, Jian (author)
- Ye, Lingying (author)
- Su, Ding-Feng (author)
- Yang, Jian (author)
- Xie, Gang (author)
- Keystone, Ed (author)
- Westra, Harm-Jan (author)
- Esko, Tonu (author)
- Metspalu, Andres (author)
- Zhou, Xuezhong (author)
- Gupta, Namrata (author)
- Mirel, Daniel (author)
- Stahl, Eli A (author)
- Diogo, Dorothee (author)
- Cui, Jing (author)
- Liao, Katherine (author)
- Guo, Michael H (author)
- Myouzen, Keiko (author)
- Kawaguchi, Takahisa (author)
- Coenen, Marieke JH (author)
- van Riel, Piet LCM (author)
- van de laar, Mart AFJ (author)
- Guchelaar, Henk-Jan (author)
- Huizinga, Tom WJ (author)
- Dieude, Philippe (author)
- Mariette, Xavier (author)
- Bridges, S Louis, Jr. (author)
- Zhernakova, Alexandra (author)
- Toes, Rene EM (author)
- Tak, Paul P (author)
- Miceli-Richard, Corinne (author)
- Bang, So-Young (author)
- Lee, Hye-Soon (author)
- Martin, Javier (author)
- Gonzalez-Gay, Miguel A (author)
- Rodriguez-Rodriguez, Luis (author)
- Choi, Hyon K (author)
- Kamatani, Yoichiro (author)
- Galan, Pilar (author)
- Lathrop, Mark (author)
- Eyre, Steve (author)
- Bowes, John (author)
- Barton, Anne (author)
- de Vries, Niek (author)
- Moreland, Larry W (author)
- Criswell, Lindsey A (author)
- Karlson, Elizabeth W (author)
- Taniguchi, Atsuo (author)
- Yamada, Ryo (author)
- Kubo, Michiaki (author)
- Liu, Jun S (author)
- Bae, Sang-Cheol (author)
- Worthington, Jane (author)
- Gregersen, Peter K (author)
- Raychaudhuri, Soumya (author)
- Stranger, Barbara E (author)
- De Jager, Philip L (author)
- Franke, Lude (author)
- Visscher, Peter M (author)
- Brown, Matthew A (author)
- Yamanaka, Hisashi (author)
- Mimori, Tsuneyo (author)
- Takahashi, Atsushi (author)
- Xu, Huji (author)
- Behrens, Timothy W (author)
- Siminovitch, Katherine A (author)
- Momohara, Shigeki (author)
- Matsuda, Fumihiko (author)
- Yamamoto, Kazuhiko (author)
- Plenge, Robert M (author)
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- (creator_code:org_t)
- 2013-12-25
- 2014
- English.
- In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
- Journal article (peer-reviewed)
Abstract
Subject headings
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- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Genome-wide association studies
- Virtual screening
Publication and Content Type
- ref (subject category)
- art (subject category)
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Find more in SwePub
- By the author/editor
- Okada, Yukinori
- Wu, Di
- Trynka, Gosia
- Raj, Towfique
- Terao, Chikashi
- Ikari, Katsunori
- show more...
- Kochi, Yuta
- Ohmura, Koichiro
- Suzuki, Akari
- Yoshida, Shinji
- Graham, Robert R
- Manoharan, Arun
- Ortmann, Ward
- Bhangale, Tushar
- Denny, Joshua C
- Carroll, Robert ...
- Eyler, Anne E
- Greenberg, Jeffr ...
- Kremer, Joel M
- Pappas, Dimitrio ...
- Jiang, Lei
- Yin, Jian
- Ye, Lingying
- Su, Ding-Feng
- Yang, Jian
- Xie, Gang
- Keystone, Ed
- Westra, Harm-Jan
- Esko, Tonu
- Metspalu, Andres
- Zhou, Xuezhong
- Gupta, Namrata
- Mirel, Daniel
- Stahl, Eli A
- Diogo, Dorothee
- Cui, Jing
- Liao, Katherine
- Guo, Michael H
- Myouzen, Keiko
- Kawaguchi, Takah ...
- Coenen, Marieke ...
- van Riel, Piet L ...
- van de laar, Mar ...
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- Huizinga, Tom WJ
- Dieude, Philippe
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- Toes, Rene EM
- Tak, Paul P
- Miceli-Richard, ...
- Bang, So-Young
- Lee, Hye-Soon
- Martin, Javier
- Gonzalez-Gay, Mi ...
- Rodriguez-Rodrig ...
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- Ärlestig, Lisbet ...
- Choi, Hyon K
- Kamatani, Yoichi ...
- Galan, Pilar
- Lathrop, Mark
- Eyre, Steve
- Bowes, John
- Barton, Anne
- de Vries, Niek
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- Taniguchi, Atsuo
- Yamada, Ryo
- Kubo, Michiaki
- Liu, Jun S
- Bae, Sang-Cheol
- Worthington, Jan ...
- Padyukov, Leonid
- Klareskog, Lars
- Gregersen, Peter ...
- Raychaudhuri, So ...
- Stranger, Barbar ...
- De Jager, Philip ...
- Franke, Lude
- Visscher, Peter ...
- Brown, Matthew A
- Yamanaka, Hisash ...
- Mimori, Tsuneyo
- Takahashi, Atsus ...
- Xu, Huji
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- Momohara, Shigek ...
- Matsuda, Fumihik ...
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- Plenge, Robert M
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- and Rheumatology and ...
- Articles in the publication
- Nature
- By the university
- Umeå University
- Karolinska Institutet
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