Genetics of rheumatoid arthritis contributes to biology and drug discovery

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Fältnamn	Indikatorer	Metadata
000		06719naa a2201489 4500
001		oai:DiVA.org:umu-87158
003		SwePub
008		140324s2014 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:128358222
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-871582 URI
024	7	a https://doi.org/10.1038/nature128732 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1283582222 URI
040		a (SwePub)umud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Okada, Yukinori4 aut
245	1 0	a Genetics of rheumatoid arthritis contributes to biology and drug discovery
264		c 2013-12-25
264	1	b Nature Publishing Group,c 2014
338		a print2 rdacarrier
520		a 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reumatologi och inflammation0 (SwePub)302102 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Rheumatology and Autoimmunity0 (SwePub)302102 hsv//eng
653		a Genome-wide association studies
653		a Virtual screening
700	1	a Wu, Di4 aut
700	1	a Trynka, Gosia4 aut
700	1	a Raj, Towfique4 aut
700	1	a Terao, Chikashi4 aut
700	1	a Ikari, Katsunori4 aut
700	1	a Kochi, Yuta4 aut
700	1	a Ohmura, Koichiro4 aut
700	1	a Suzuki, Akari4 aut
700	1	a Yoshida, Shinji4 aut
700	1	a Graham, Robert R4 aut
700	1	a Manoharan, Arun4 aut
700	1	a Ortmann, Ward4 aut
700	1	a Bhangale, Tushar4 aut
700	1	a Denny, Joshua C4 aut
700	1	a Carroll, Robert J4 aut
700	1	a Eyler, Anne E4 aut
700	1	a Greenberg, Jeffrey D4 aut
700	1	a Kremer, Joel M4 aut
700	1	a Pappas, Dimitrios A4 aut
700	1	a Jiang, Lei4 aut
700	1	a Yin, Jian4 aut
700	1	a Ye, Lingying4 aut
700	1	a Su, Ding-Feng4 aut
700	1	a Yang, Jian4 aut
700	1	a Xie, Gang4 aut
700	1	a Keystone, Ed4 aut
700	1	a Westra, Harm-Jan4 aut
700	1	a Esko, Tonu4 aut
700	1	a Metspalu, Andres4 aut
700	1	a Zhou, Xuezhong4 aut
700	1	a Gupta, Namrata4 aut
700	1	a Mirel, Daniel4 aut
700	1	a Stahl, Eli A4 aut
700	1	a Diogo, Dorothee4 aut
700	1	a Cui, Jing4 aut
700	1	a Liao, Katherine4 aut
700	1	a Guo, Michael H4 aut
700	1	a Myouzen, Keiko4 aut
700	1	a Kawaguchi, Takahisa4 aut
700	1	a Coenen, Marieke JH4 aut
700	1	a van Riel, Piet LCM4 aut
700	1	a van de laar, Mart AFJ4 aut
700	1	a Guchelaar, Henk-Jan4 aut
700	1	a Huizinga, Tom WJ4 aut
700	1	a Dieude, Philippe4 aut
700	1	a Mariette, Xavier4 aut
700	1	a Bridges, S Louis, Jr.4 aut
700	1	a Zhernakova, Alexandra4 aut
700	1	a Toes, Rene EM4 aut
700	1	a Tak, Paul P4 aut
700	1	a Miceli-Richard, Corinne4 aut
700	1	a Bang, So-Young4 aut
700	1	a Lee, Hye-Soon4 aut
700	1	a Martin, Javier4 aut
700	1	a Gonzalez-Gay, Miguel A4 aut
700	1	a Rodriguez-Rodriguez, Luis4 aut
700	1	a Rantapää-Dahlqvist, Solbrittu Umeå universitet,Reumatologi4 aut0 (Swepub:umu)sora0001
700	1	a Ärlestig, Lisbethu Umeå universitet,Reumatologi4 aut0 (Swepub:umu)litarg99
700	1	a Choi, Hyon K4 aut
700	1	a Kamatani, Yoichiro4 aut
700	1	a Galan, Pilar4 aut
700	1	a Lathrop, Mark4 aut
700	1	a Eyre, Steve4 aut
700	1	a Bowes, John4 aut
700	1	a Barton, Anne4 aut
700	1	a de Vries, Niek4 aut
700	1	a Moreland, Larry W4 aut
700	1	a Criswell, Lindsey A4 aut
700	1	a Karlson, Elizabeth W4 aut
700	1	a Taniguchi, Atsuo4 aut
700	1	a Yamada, Ryo4 aut
700	1	a Kubo, Michiaki4 aut
700	1	a Liu, Jun S4 aut
700	1	a Bae, Sang-Cheol4 aut
700	1	a Worthington, Jane4 aut
700	1	a Padyukov, Leonidu Karolinska Institutet4 aut
700	1	a Klareskog, Larsu Karolinska Institutet4 aut
700	1	a Gregersen, Peter K4 aut
700	1	a Raychaudhuri, Soumya4 aut
700	1	a Stranger, Barbara E4 aut
700	1	a De Jager, Philip L4 aut
700	1	a Franke, Lude4 aut
700	1	a Visscher, Peter M4 aut
700	1	a Brown, Matthew A4 aut
700	1	a Yamanaka, Hisashi4 aut
700	1	a Mimori, Tsuneyo4 aut
700	1	a Takahashi, Atsushi4 aut
700	1	a Xu, Huji4 aut
700	1	a Behrens, Timothy W4 aut
700	1	a Siminovitch, Katherine A4 aut
700	1	a Momohara, Shigeki4 aut
700	1	a Matsuda, Fumihiko4 aut
700	1	a Yamamoto, Kazuhiko4 aut
700	1	a Plenge, Robert M4 aut
710	2	a Umeå universitetb Reumatologi4 org
773	0	t Natured : Nature Publishing Groupg 506:7488, s. 376-381q 506:7488<376-381x 0028-0836x 1476-4687
856	4	u https://europepmc.org/articles/pmc3944098?pdf=render
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-87158
856	4 8	u https://doi.org/10.1038/nature12873
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:128358222

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Av författaren/redakt...: Okada, Yukinori; Wu, Di; Trynka, Gosia; Raj, Towfique; Terao, Chikashi; Ikari, Katsunori; visa fler...; 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 ...; Guchelaar, Henk- ...; Huizinga, Tom WJ; Dieude, Philippe; Mariette, Xavier; Bridges, S Louis ...; Zhernakova, Alex ...; Toes, Rene EM; Tak, Paul P; Miceli-Richard, ...; Bang, So-Young; Lee, Hye-Soon; Martin, Javier; Gonzalez-Gay, Mi ...; Rodriguez-Rodrig ...; Rantapää-Dahlqvi ...; Ärlestig, Lisbet ...; Choi, Hyon K; Kamatani, Yoichi ...; Galan, Pilar; Lathrop, Mark; Eyre, Steve; Bowes, John; Barton, Anne; de Vries, Niek; Moreland, Larry ...; Criswell, Lindse ...; Karlson, Elizabe ...; 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; Behrens, Timothy ...; Siminovitch, Kat ...; Momohara, Shigek ...; Matsuda, Fumihik ...; Yamamoto, Kazuhi ...; Plenge, Robert M; visa färre...

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