Differential methylation of the TRPA1 promoter in pain sensitivity.
Differential methylation of the TRPA1 promoter in pain sensitivity.
复制标题
DOI：
10.1038/ncomms3978
复制
发表时间：
2014
影响因子：
16.6
通讯作者：
Spector, T. D.
中科院分区：
文献类型：
--
作者：
Bell, J. T.;Loomis, A. K.;Butcher, L. M.;Gao, F.;Zhang, B.;Hyde, C. L.;Sun, J.;Wu, H.;Ward, K.;Harris, J.;Scollen, S.;Davies, M. N.;Schalkwyk, L. C.;Mill, J.;Williams, F. M. K.;Li, N.;Deloukas, P.;Beck, S.;McMahon, S. B.;Wang, J.;John, S. L.;Spector, T. D.
慢性疼痛是一个全球性的公共卫生问题，但其潜在的分子机制尚未完全了解。在这里，我们研究了全基因组DNA甲基化，首先在50对热痛敏感性不一致的同卵双胞胎中，然后在另外50个无关个体中。通过MeDIP测序在520万个位点上表征全血DNA甲基化，并纵向评估以鉴定与高或低疼痛敏感性（疼痛DMR）相关的差异甲基化区域。9项荟萃分析疼痛DMR显示了与疼痛基因TRPA1中最强信号相关的强有力证据（错误发现率5%）（P=1.2 × 10−13）。几种疼痛DMR显示出与易感性效应一致的纵向稳定性，在大脑中具有相似的甲基化水平，在皮肤中具有改变的表达。我们的方法确定了新的和已建立的候选基因中的表观遗传变化，这些基因提供了对疼痛的分子见解，并可能推广到其他复杂的性状。 同卵双胞胎为识别与复杂性状相关的表观遗传因素提供了宝贵的资源。在这里，作者采用了这种方法，发现疼痛基因TRPA1的差异甲基化与人类的疼痛敏感性有关。
Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole-blood DNA methylation was characterized at 5.2 million loci by MeDIP sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain sensitivity (pain DMRs). Nine meta-analysis pain DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2 × 10−13). Several pain DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in the brain and altered expression in the skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits. Genetically identical twins provide a valuable resource to identify epigenetic factors associated with complex traits. Here the authors adopt this approach and find that differential methylation of the pain gene TRPA1 is associated with pain sensitivity in humans.
登录
查看更多内容
影响因子：
3.5
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
通讯作者：
Mill J
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：
30.8
作者：
通讯作者：
--
影响因子：
25
作者：
Kirilly, Daniel;Gu, Ying;Yu, Fengwei
通讯作者：
Yu, Fengwei
影响因子：
3.7
作者：
Lee KT;Byun MJ;Kang KS;Park EW;Lee SH;Cho S;Kim H;Kim KW;Lee T;Park JE;Park W;Shin D;Park HS;Jeon JT;Choi BH;Jang GW;Choi SH;Kim DW;Lim D;Park HS;Park MR;Ott J;Schook LB;Kim TH;Kim H
通讯作者：
Kim H