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Novel risk genes fo...
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Carlsson Almlöf, JonasUppsala universitet,Uppsala University,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden
(author)
Novel risk genes for systemic lupus erythematosus predicted by random forest classification
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-07-24
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Springer Science and Business Media LLC,2017
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:bd995694-7e1b-4159-a59e-0b517a30be71
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https://lup.lub.lu.se/record/bd995694-7e1b-4159-a59e-0b517a30be71URI
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https://doi.org/10.1038/s41598-017-06516-1DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-138601URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:136395300URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-333524URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-140068URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Funding Agencies|Knut and Alice Wallenberg Foundation; Swedish Research Council for Medicine and Health [521-2014-2263, 521-2013-2830]; Swedish Rheumatism Association; King Gustaf V 80-year Foundation; COMBINE
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Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Bengtsson, Anders A.Uppsala universitet,Lund University,Lunds universitet,Uppsala University,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital,Reumatologi,Science for Life Laboratory, SciLifeLab,Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden.,Uppsala University, Sweden,Lund University, Sweden(Swepub:uu)andax639
(author)
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Imgenberg-Kreuz, JulianaUppsala universitet,Uppsala University,Science for Life Laboratory, SciLifeLab,Molekylär medicin,Uppsala University, Sweden(Swepub:uu)julim920
(author)
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Sylwan, LinaUppsala University,Karolinska Institute,Karolinska Inst, Dept Biosci & Nutr, Sci Life Lab SciLifeLab, Solna, Sweden.,Uppsala University, Sweden; Karolinska Institute, Sweden
(author)
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Bäcklin, Christofer,1983-Uppsala universitet,Uppsala University,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)chrba104
(author)
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Leonard, Dag,1975-Uppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)dagle338
(author)
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Nordmark, GunnelUppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)gunnnord
(author)
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Tandre, KarolinaUppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)karotand
(author)
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Eloranta, Maija-LeenaUppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)maelo020
(author)
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Padyukov, LeonidKarolinska Institutet,Karolinska University Hospital, Sweden,Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
(author)
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Bengtsson, ChristineUmeå universitet,Umeå University,Reumatologi,Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden.,Umeå University, Sweden(Swepub:umu)chbe0055
(author)
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Jönsen, AndreasLund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital,Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden.,Lund University, Sweden(Swepub:lu)reum-ajo
(author)
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Dahlqvist, Solbritt RantapaaUmeå universitet,Umeå University,Reumatologi,Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden.,Umeå University, Sweden(Swepub:umu)sora0001
(author)
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Sjöwall, ChristopherLinköpings universitet,Linköping University,Linkoping Univ, Dept Clin & Expt Med, AIR Rheumatol, Linkoping, Sweden.,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland(Swepub:liu)chrsj93
(author)
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Bengtsson, Anders A.Lund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)reum-abe
(author)
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Gunnarsson, IvaKarolinska Institutet,Karolinska University Hospital, Sweden,Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
(author)
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Svenungsson, ElisabetKarolinska Institutet,Karolinska University Hospital, Sweden,Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
(author)
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Rönnblom, LarsUppsala universitet,Uppsala University,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)larsronn
(author)
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Sandling, Johanna K.Uppsala universitet,Uppsala University,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Reumatologi,Uppsala University, Sweden; Uppsala University, Sweden(Swepub:uu)josan062
(author)
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Syvänen, Ann-Christine,1950-Uppsala universitet,Uppsala University,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Uppsala University, Sweden(Swepub:uu)anncsyva
(author)
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Uppsala UniversityMolekylär medicin
(creator_code:org_t)
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In:Scientific Reports: Springer Science and Business Media LLC7:12045-2322
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