Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci.
Long-range epigenetic regulation is conferred by genetic variation located at thousands of independent loci.
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DOI：
10.1038/ncomms7326
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发表时间：
2015-02-26
影响因子：
16.6
通讯作者：
Hudson, Thomas J.
中科院分区：
文献类型：
--
作者：
Lemire, Mathieu;Zaidi, Syed H. E.;Ban, Maria;Ge, Bing;Aissi, Dylan;Germain, Marine;Kassam, Irfahan;Wang, Mike;Zanke, Brent W.;Gagnon, France;Morange, Pierre-Emmanuel;Tregouet, David-Alexandre;Wells, Philip S.;Sawcer, Stephen;Gallinger, Steven;Pastinen, Tomi;Hudson, Thomas J.
遗传变异和表观遗传变异之间的相互作用只被部分理解。表观遗传变异的一种形式是CpG位点的甲基化，其可以被测量为甲基化数量性状基因座（meQTL）。在这里，我们报告说，在一组来自1,748个个体的淋巴细胞中，1,919个CpG位点的甲基化水平与至少一个远端（反式）单核苷酸多态性（SNP）相关（P<3.2 × 10−13; FDR<5%）。这些trans-meQTL包括来自不同染色体的1，657个SNP-CpG对和来自相同染色体的262个相距>1 Mb的SNP-CpG对。超过90%的这些对在两个独立数据集中的至少一个中被复制（FDR<5%）。携带trans-meQTL的基因组位点显著富集（P<0.001）长非编码转录物（2.2倍）、已知的表观遗传调节因子（2.3倍）、piwi相互作用RNA簇（3.6倍）和策划的转录因子（4.1倍），包括锌指蛋白（8.75倍）。这种方法发现的远程表观遗传网络可能与正常和疾病状态有关。 当SNP和表观遗传变异处于近距离时，它们之间存在功能联系，但长期效应尚不清楚。在这里，通过分析甲基化数量性状基因座，作者证明了淋巴细胞中CpG位点的甲基化水平与远端SNP相关。
The interplay between genetic and epigenetic variation is only partially understood. One form of epigenetic variation is methylation at CpG sites, which can be measured as methylation quantitative trait loci (meQTL). Here we report that in a panel of lymphocytes from 1,748 individuals, methylation levels at 1,919 CpG sites are correlated with at least one distal (trans) single-nucleotide polymorphism (SNP) (P<3.2 × 10−13; FDR<5%). These trans-meQTLs include 1,657 SNP–CpG pairs from different chromosomes and 262 pairs from the same chromosome that are >1 Mb apart. Over 90% of these pairs are replicated (FDR<5%) in at least one of two independent data sets. Genomic loci harbouring trans-meQTLs are significantly enriched (P<0.001) for long non-coding transcripts (2.2-fold), known epigenetic regulators (2.3-fold), piwi-interacting RNA clusters (3.6-fold) and curated transcription factors (4.1-fold), including zinc-finger proteins (8.75-fold). Long-range epigenetic networks uncovered by this approach may be relevant to normal and disease states. There is a functional link between SNPs and epigenetic variations when they are in close range, but the long-range effect is unclear. Here, by analysing methylation quantitative trait loci, the authors demonstrate that methylation levels at CpG sites in lymphocytes are correlated with distal SNPs.
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影响因子：
7.7
作者：
Gutierrez-Arcelus M;Lappalainen T;Montgomery SB;Buil A;Ongen H;Yurovsky A;Bryois J;Giger T;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Padioleau I;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
通讯作者：
Dermitzakis ET
影响因子：
7
作者：
Battle A;Mostafavi S;Zhu X;Potash JB;Weissman MM;McCormick C;Haudenschild CD;Beckman KB;Shi J;Mei R;Urban AE;Montgomery SB;Levinson DF;Koller D
通讯作者：
Koller D
影响因子：
168.9
作者：
Dick, Katherine J.;Nelson, Christopher P.;Samani, Nilesh J.
通讯作者：
Samani, Nilesh J.
DOI：
10.1158/1055-9965.epi-12-0361
发表时间：
2012-08
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Koestler DC;Marsit CJ;Christensen BC;Accomando W;Langevin SM;Houseman EA;Nelson HH;Karagas MR;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
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