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Genetics of rheumat...
Genetics of rheumatoid arthritis contributes to biology and drug discovery
- Article/chapterEnglish2014
Publisher, publication year, extent ...
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2013-12-25
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Nature Publishing Group,2014
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-87158
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-87158URI
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https://doi.org/10.1038/nature12873DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:128358222URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Wu, Di
(author)
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Trynka, Gosia
(author)
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Raj, Towfique
(author)
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Terao, Chikashi
(author)
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Ikari, Katsunori
(author)
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Kochi, Yuta
(author)
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Ohmura, Koichiro
(author)
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Suzuki, Akari
(author)
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Yoshida, Shinji
(author)
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Graham, Robert R
(author)
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Manoharan, Arun
(author)
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Ortmann, Ward
(author)
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Bhangale, Tushar
(author)
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Denny, Joshua C
(author)
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Carroll, Robert J
(author)
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Eyler, Anne E
(author)
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Greenberg, Jeffrey D
(author)
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Kremer, Joel M
(author)
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Pappas, Dimitrios A
(author)
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Jiang, Lei
(author)
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Yin, Jian
(author)
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Ye, Lingying
(author)
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Su, Ding-Feng
(author)
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Yang, Jian
(author)
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Xie, Gang
(author)
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Keystone, Ed
(author)
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Westra, Harm-Jan
(author)
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Esko, Tonu
(author)
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Metspalu, Andres
(author)
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Zhou, Xuezhong
(author)
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Gupta, Namrata
(author)
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Mirel, Daniel
(author)
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Stahl, Eli A
(author)
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Diogo, Dorothee
(author)
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Cui, Jing
(author)
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Liao, Katherine
(author)
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Guo, Michael H
(author)
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Myouzen, Keiko
(author)
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Kawaguchi, Takahisa
(author)
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Coenen, Marieke JH
(author)
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van Riel, Piet LCM
(author)
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van de laar, Mart AFJ
(author)
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Guchelaar, Henk-Jan
(author)
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Huizinga, Tom WJ
(author)
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Dieude, Philippe
(author)
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Mariette, Xavier
(author)
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Bridges, S Louis, Jr.
(author)
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Zhernakova, Alexandra
(author)
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Toes, Rene EM
(author)
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Tak, Paul P
(author)
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Miceli-Richard, Corinne
(author)
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Bang, So-Young
(author)
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Lee, Hye-Soon
(author)
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Martin, Javier
(author)
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Gonzalez-Gay, Miguel A
(author)
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Rodriguez-Rodriguez, Luis
(author)
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Rantapää-Dahlqvist, SolbrittUmeå universitet,Reumatologi(Swepub:umu)sora0001
(author)
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Ärlestig, LisbethUmeå universitet,Reumatologi(Swepub:umu)litarg99
(author)
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Choi, Hyon K
(author)
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Kamatani, Yoichiro
(author)
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Galan, Pilar
(author)
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Lathrop, Mark
(author)
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Eyre, Steve
(author)
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Bowes, John
(author)
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Barton, Anne
(author)
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de Vries, Niek
(author)
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Moreland, Larry W
(author)
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Criswell, Lindsey A
(author)
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Karlson, Elizabeth W
(author)
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Taniguchi, Atsuo
(author)
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Yamada, Ryo
(author)
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Kubo, Michiaki
(author)
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Liu, Jun S
(author)
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Bae, Sang-Cheol
(author)
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Worthington, Jane
(author)
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Padyukov, LeonidKarolinska Institutet
(author)
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Klareskog, LarsKarolinska Institutet
(author)
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Gregersen, Peter K
(author)
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Raychaudhuri, Soumya
(author)
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Stranger, Barbara E
(author)
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De Jager, Philip L
(author)
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Franke, Lude
(author)
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Visscher, Peter M
(author)
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Brown, Matthew A
(author)
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Yamanaka, Hisashi
(author)
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Mimori, Tsuneyo
(author)
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Takahashi, Atsushi
(author)
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Xu, Huji
(author)
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Behrens, Timothy W
(author)
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Siminovitch, Katherine A
(author)
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Momohara, Shigeki
(author)
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Matsuda, Fumihiko
(author)
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Yamamoto, Kazuhiko
(author)
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Plenge, Robert M
(author)
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Umeå universitetReumatologi
(creator_code:org_t)
Related titles
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In:Nature: Nature Publishing Group506:7488, s. 376-3810028-08361476-4687
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To the university's database
- By the author/editor
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Okada, Yukinori
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Wu, Di
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Trynka, Gosia
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Raj, Towfique
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Terao, Chikashi
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Ikari, Katsunori
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show more...
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Kochi, Yuta
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Ohmura, Koichiro
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Suzuki, Akari
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Yoshida, Shinji
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Graham, Robert R
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Manoharan, Arun
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Ortmann, Ward
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Bhangale, Tushar
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Denny, Joshua C
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Carroll, Robert ...
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Eyler, Anne E
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Greenberg, Jeffr ...
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Kremer, Joel M
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Pappas, Dimitrio ...
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Jiang, Lei
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Yin, Jian
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Ye, Lingying
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Su, Ding-Feng
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Yang, Jian
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Xie, Gang
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Keystone, Ed
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Westra, Harm-Jan
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Esko, Tonu
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Metspalu, Andres
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Zhou, Xuezhong
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Gupta, Namrata
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Mirel, Daniel
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Stahl, Eli A
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Diogo, Dorothee
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Cui, Jing
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Liao, Katherine
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Guo, Michael H
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Myouzen, Keiko
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Kawaguchi, Takah ...
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Coenen, Marieke ...
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van Riel, Piet L ...
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van de laar, Mar ...
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Guchelaar, Henk- ...
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Huizinga, Tom WJ
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Dieude, Philippe
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Mariette, Xavier
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Bridges, S Louis ...
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Zhernakova, Alex ...
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Toes, Rene EM
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Tak, Paul P
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Miceli-Richard, ...
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Bang, So-Young
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Lee, Hye-Soon
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Martin, Javier
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Gonzalez-Gay, Mi ...
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Rodriguez-Rodrig ...
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Rantapää-Dahlqvi ...
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Ärlestig, Lisbet ...
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Choi, Hyon K
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Kamatani, Yoichi ...
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Galan, Pilar
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Lathrop, Mark
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Eyre, Steve
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Bowes, John
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Barton, Anne
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de Vries, Niek
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Moreland, Larry ...
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Criswell, Lindse ...
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Karlson, Elizabe ...
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Taniguchi, Atsuo
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Yamada, Ryo
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Kubo, Michiaki
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Liu, Jun S
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Bae, Sang-Cheol
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Worthington, Jan ...
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Padyukov, Leonid
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Klareskog, Lars
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Gregersen, Peter ...
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Raychaudhuri, So ...
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Stranger, Barbar ...
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De Jager, Philip ...
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Franke, Lude
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Visscher, Peter ...
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Brown, Matthew A
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Yamanaka, Hisash ...
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Mimori, Tsuneyo
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Takahashi, Atsus ...
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Xu, Huji
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Behrens, Timothy ...
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Siminovitch, Kat ...
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Momohara, Shigek ...
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Matsuda, Fumihik ...
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Yamamoto, Kazuhi ...
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Plenge, Robert M
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
- Articles in the publication
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Nature
- By the university
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Umeå University
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Karolinska Institutet