Disease-specific regulation of gene expression in a comparative analysis of juvenile idiopathic arthritis and inflammatory bowel disease.
Disease-specific regulation of gene expression in a comparative analysis of juvenile idiopathic arthritis and inflammatory bowel disease.
复制标题
DOI：
10.1186/s13073-018-0558-x
复制
发表时间：
2018-06-27
期刊：
影响因子：
12.3
通讯作者：
Gibson G
中科院分区：
文献类型：
--
作者：
Mo A;Marigorta UM;Arafat D;Chan LHK;Ponder L;Jang SR;Prince J;Kugathasan S;Prahalad S;Gibson G
The genetic and immunological factors that contribute to differences in susceptibility and progression between sub-types of inflammatory and autoimmune diseases continue to be elucidated. Inflammatory bowel disease and juvenile idiopathic arthritis are both clinically heterogeneous and known to be due in part to abnormal regulation of gene activity in diverse immune cell types. Comparative genomic analysis of these conditions is expected to reveal differences in underlying genetic mechanisms of disease. We performed RNA-Seq on whole blood samples from 202 patients with oligoarticular, polyarticular, or systemic juvenile idiopathic arthritis, or with Crohn’s disease or ulcerative colitis, as well as healthy controls, to characterize differences in gene expression. Gene ontology analysis combined with Blood Transcript Module and Blood Informative Transcript analysis was used to infer immunological differences. Comparative expression quantitative trait locus (eQTL) analysis was used to quantify disease-specific regulation of transcript abundance. A pattern of differentially expressed genes and pathways reveals a gradient of disease spanning from healthy controls to oligoarticular, polyarticular, and systemic juvenile idiopathic arthritis (JIA); Crohn’s disease; and ulcerative colitis. Transcriptional risk scores also provide good discrimination of controls, JIA, and IBD. Most eQTL are found to have similar effects across disease sub-types, but we also identify disease-specific eQTL at loci associated with disease by GWAS. JIA and IBD are characterized by divergent peripheral blood transcriptomes, the genetic regulation of which displays limited disease specificity, implying that disease-specific genetic influences are largely independent of, or downstream of, eQTL effects. The online version of this article (10.1186/s13073-018-0558-x) contains supplementary material, which is available to authorized users.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
30.8
作者：
Hinks, Anne;Cobb, Joanna;Marion, Miranda C.;Prahalad, Sampath;Sudman, Marc;Bowes, John;Martin, Paul;Comeau, Mary E.;Sajuthi, Satria;Andrews, Robert;Brown, Milton;Chen, Wei-Min;Concannon, Patrick;Deloukas, Panos;Edkins, Sarah;Eyre, Stephen;Gaffney, Patrick M.;Guthery, Stephen L.;Guthridge, Joel M.;Hunt, Sarah E.;James, Judith A.;Keddache, Mehdi;Moser, Kathy L.;Nigrovic, Peter A.;Onengut-Gumuscu, Suna;Onslow, Mitchell L.;Rose, Carlos D.;Rich, Stephen S.;Steel, Kathryn J. A.;Wakeland, Edward K.;Wallace, Carol A.;Wedderburn, Lucy R.;Woo, Patricia;Bohnsack, John F.;Haas, Johannes Peter;Glass, David N.;Langefeld, Carl D.;Thomson, Wendy;Thompson, Susan D.
通讯作者：
Thompson, Susan D.
影响因子：
--
作者：
Griffin, Thomas A.;Barnes, Michael G.;Ilowite, Norman T.;Olson, Judyann C.;Sherry, David D.;Gottlieb, Beth S.;Aronow, Bruce J.;Pavlidis, Paul;Hinze, Claas. H.;Thornton, Sherry;Thompson, Susan D.;Grom, Alexei A.;Colbert, Robert A.;Glass, David N.
通讯作者：
Glass, David N.
影响因子：
30.8
作者：
Fairfax, Benjamin P.;Makino, Seiko;Radhakrishnan, Jayachandran;Plant, Katharine;Leslie, Stephen;Dilthey, Alexander;Ellis, Peter;Langford, Cordelia;Vannberg, Fredrik O.;Knight, Julian C.
通讯作者：
Knight, Julian C.
影响因子：
30.8
作者：
Ellinghaus D;Jostins L;Spain SL;Cortes A;Bethune J;Han B;Park YR;Raychaudhuri S;Pouget JG;Hübenthal M;Folseraas T;Wang Y;Esko T;Metspalu A;Westra HJ;Franke L;Pers TH;Weersma RK;Collij V;D'Amato M;Halfvarson J;Jensen AB;Lieb W;Degenhardt F;Forstner AJ;Hofmann A;International IBD Genetics Consortium (IIBDGC);International Genetics of Ankylosing Spondylitis Consortium (IGAS);International PSC Study Group (IPSCSG);Genetic Analysis of Psoriasis Consortium (GAPC);Psoriasis Association Genetics Extension (PAGE);Schreiber S;Mrowietz U;Juran BD;Lazaridis KN;Brunak S;Dale AM;Trembath RC;Weidinger S;Weichenthal M;Ellinghaus E;Elder JT;Barker JN;Andreassen OA;McGovern DP;Karlsen TH;Barrett JC;Parkes M;Brown MA;Franke A
通讯作者：
Franke A