Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.
Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.
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DOI：
10.1002/art.38137
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发表时间：
2013-12
影响因子：
--
通讯作者：
Gregersen, Peter K.
中科院分区：
文献类型：
--
作者：
Miller, Frederick W.;Cooper, Robert G.;Vencovsky, Jiri;Rider, Lisa G.;Danko, Katalin;Wedderburn, Lucy R.;Lundberg, Ingrid E.;Pachman, Lauren M.;Reed, Ann M.;Ytterberg, Steven R.;Padyukov, Leonid;Selva-O'Callaghan, Albert;Radstake, Timothy R. D. J.;Isenberg, David A.;Chinoy, Hector;Ollier, William E. R.;O'Hanlon, Terrance P.;Peng, Bo;Lee, Annette;Lamb, Janine A.;Chen, Wei;Amos, Christopher I.;Gregersen, Peter K.
目的：确定与青少年和成人皮肌炎（DM）的新的遗传关联。我们对欧洲血统的成人和青少年DM患者（n = 1178）和对照组（n = 4724）进行了全基因组关联研究（GWAS）。为了评估与其他自身免疫性疾病的遗传重叠，我们研究了主要组织相容性复合体（MHC）基因座外的141个单核苷酸多态性（SNP）是否与自身免疫性疾病相关，易患DM。与对照组相比，DM患者在MHC区域有一个强信号，在80个基因型SNP上具有GWAS水平的显著性（P <5x 10 −8）。对先前与自身免疫性疾病相关的141个非MHC SNPs的分析显示，与三个基因连锁的三个SNPs与DM相关，错误发现率（FDR）< 0.05。这些基因是磷脂酶C样1（PLCL 1，rs6738825，FDR=0.00089）、B淋巴酪氨酸激酶（BLK，rs 2736340，FDR=0.00031）和趋化因子（C-C基序）配体21（CCL 21，rs 951005，FDR=0.0076）。这些基因中没有一个先前被报道与DM相关。我们的研究结果证实了MHC是与DM相关的主要遗传区域，并表明DM与其他自身免疫性疾病具有非MHC遗传特征，表明存在其他新的风险位点。这一首次发现的自身免疫性疾病遗传易感性与糖尿病共享，可能会导致增强了解的发病机制和新的诊断和治疗方法。
To identify new genetic associations with juvenile and adult dermatomyositis (DM). We performed a genome-wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1178) and controls (n = 4724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM. Compared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS-level significance (P < 5x10−8) at 80 genotyped SNPs. An analysis of 141 non-MHC SNPs previously associated with autoimmune diseases showed that three SNPs linked with three genes were associated with DM, with a false discovery rate (FDR) < 0.05. These genes were phospholipase C like 1 (PLCL1, rs6738825, FDR=0.00089), B lymphoid tyrosine kinase (BLK, rs2736340, FDR=0.00031), and chemokine (C-C motif) ligand 21 (CCL21, rs951005, FDR=0.0076). None of these genes was previously reported to be associated with DM. Our findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non-MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches.
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影响因子：
5
作者：
Nordmark, G.;Kristjansdottir, G.;Syvanen, A-C
通讯作者：
Syvanen, A-C
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
4.9
作者：
Nanki T;Takada K;Komano Y;Morio T;Kanegane H;Nakajima A;Lipsky PE;Miyasaka N
通讯作者：
Miyasaka N
影响因子：
4.9
作者：
Chinoy H;Lamb JA;Ollier WE;Cooper RG
通讯作者：
Cooper RG
DOI：
10.1038/nrrheum.2010.176
发表时间：
2010-12
期刊：
Nature reviews. Rheumatology
影响因子：
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作者：
通讯作者：
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