Disease-Associated Single-Nucleotide Polymorphisms From Noncoding Regions in Juvenile Idiopathic Arthritis Are Located Within or Adjacent to Functional Genomic Elements of Human Neutrophils and CD4+ T Cells.
Disease-Associated Single-Nucleotide Polymorphisms From Noncoding Regions in Juvenile Idiopathic Arthritis Are Located Within or Adjacent to Functional Genomic Elements of Human Neutrophils and CD4+ T Cells.
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DOI：
10.1002/art.39135
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发表时间：
2015-07
影响因子：
13.3
通讯作者：
Jarvis, James N.
中科院分区：
文献类型：
--
作者：
Jiang, Kaiyu;Zhu, Lisha;Buck, Michael J.;Chen, Yanmin;Carrier, Bradley;Liu, Tao;Jarvis, James N.
Juvenile idiopathic arthritis (JIA) is considered a complex trait in which the environment interacts with inherited genes to produce a phenotype that shows broad inter-individual variance. A recently completed genome-wide association study (GWAS) identified 24 regions of genetic risk for JIA, for example. However, as is typical for GWAS, most of the regions of genetic risk for JIA (22 of 24) were in non-coding regions of the genome. The studies reported here were undertaken to identify functional elements (other than genes) that might be located within the regions of genetic risk. We used paired end RNA sequencing to identify non-coding RNAs located within 5 kb of the disease-associated SNPs. In addition, we used chromatin immunoprecipitation-sequencing (ChIP-Seq) to identify epigenetic marks associated with enhancer function (H3K4me1 and H3K27ac) in human neutrophils to determine whether there was enrichment of enhancer-associated histone marks in linkage disequilibrium (LD) blocks that encompassed the 22 GWAS SNPs from the non-coding genome. In human neutrophils, we identified H3K4me1 and/or H3K27ac marks in 15 of the 22 regions previously as identified as risk loci for JIA. In CD4+ T cells, 18 regions demonstrate H3K4me1 and/or H3K27ac marks. In addition, we identified non-coding RNA transcripts at the rs4705862 and rs6894249 loci in human neutrophils. Much of the genetic risk for JIA lies within or adjacent to regions of neutrophil and CD4+ T cell genomes that carry epigenetic marks associated with enhancer function and/or ncRNA transcripts. These findings are consistent with the hypothesis that JIA is fundamentally a disorder of gene regulation that includes both the innate and adaptive immune system. Elucidating the specific roles of these non-coding elements within leukocyte genomes in JIA pathogenesis will be critical to our understanding disease pathogenesis.
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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.
中性粒细胞：Jia病发病机理中被遗忘的细胞。
影响因子：
2.5
作者：
Jarvis, James N;Jiang, Kaiyu;Petty, Howard R;Centola, Michael
通讯作者：
Centola, Michael
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
DOI：
10.1126/science.1222794
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maurano MT;Humbert R;Rynes E;Thurman RE;Haugen E;Wang H;Reynolds AP;Sandstrom R;Qu H;Brody J;Shafer A;Neri F;Lee K;Kutyavin T;Stehling-Sun S;Johnson AK;Canfield TK;Giste E;Diegel M;Bates D;Hansen RS;Neph S;Sabo PJ;Heimfeld S;Raubitschek A;Ziegler S;Cotsapas C;Sotoodehnia N;Glass I;Sunyaev SR;Kaul R;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA