Increased DNA methylation variability in rheumatoid arthritis-discordant monozygotic twins.
Increased DNA methylation variability in rheumatoid arthritis-discordant monozygotic twins.
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DOI：
10.1186/s13073-018-0575-9
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发表时间：
2018-09-04
期刊：
影响因子：
12.3
通讯作者：
Worthington J
中科院分区：
文献类型：
--
作者：
Webster AP;Plant D;Ecker S;Zufferey F;Bell JT;Feber A;Paul DS;Beck S;Barton A;Williams FMK;Worthington J
类风湿性关节炎是一种常见的自身免疫性疾病，受遗传和环境因素的影响。全表观基因组关联研究可以识别环境介导的表观遗传变化，如DNA甲基化改变，这也可能受到遗传因素的影响。为了研究DNA甲基化对类风湿关节炎病因学的可能贡献，同时最小化混杂遗传异质性，我们研究了疾病不一致的单卵双胞胎的全基因组DNA甲基化。使用HumanMethylation450头芯片阵列（Illumina）对79对类风湿关节炎不一致的单卵双胞胎进行全基因组DNA甲基化评估。对不一致的双胞胎进行了类风湿关节炎和健康双胞胎之间差异DNA甲基化和甲基化变异性的测试。然后将甲基化变异性特征与其他自身免疫性疾病研究中的甲基化变异以及独立的健康人群进行比较。我们已经确定了一个差异可变的DNA甲基化特征，表明多种应激反应途径可能参与疾病的病因学。这种甲基化变异性特征也突出了多个RUNX3转录因子结合位点的潜在表观遗传破坏与疾病发展相关。与先前进行的类风湿性关节炎和1型糖尿病的全表观基因组关联研究比较，发现了自身免疫性疾病的共同途径，表明表观遗传学在自身免疫中起作用，并提供了确定新的干预靶点的可能性。通过对疾病不一致的同卵双胞胎的DNA甲基化的全基因组分析，我们已经确定了在类风湿关节炎中没有差异甲基化的差异可变DNA甲基化特征。这一发现支持了表观遗传变异性作为自身免疫性疾病新组成部分的重要性。本文的在线版本（10.1186/s13073-018-0575-9）包含补充材料，授权用户可使用。
Rheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs. Genome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between rheumatoid arthritis and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population. We have identified a differentially variable DNA methylation signature that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention. Through genome-wide analysis of DNA methylation in disease-discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders. The online version of this article (10.1186/s13073-018-0575-9) contains supplementary material, which is available to authorized users.
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影响因子：
16.6
作者：
Guilhamon P;Eskandarpour M;Halai D;Wilson GA;Feber A;Teschendorff AE;Gomez V;Hergovich A;Tirabosco R;Fernanda Amary M;Baumhoer D;Jundt G;Ross MT;Flanagan AM;Beck S
通讯作者：
Beck S
DOI：
10.1038/nrg2881
发表时间：
2010-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
12.3
作者：
Gomez-Cabrero D;Almgren M;Sjöholm LK;Hensvold AH;Ringh MV;Tryggvadottir R;Kere J;Scheynius A;Acevedo N;Reinius L;Taub MA;Montano C;Aryee MJ;Feinberg JI;Feinberg AP;Tegnér J;Klareskog L;Catrina AI;Ekström TJ
通讯作者：
Ekström TJ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.8
作者：
Geeleher, Paul;Hartnett, Lori;Seoighe, Cathal
通讯作者：
Seoighe, Cathal