Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence.
Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence.
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DOI：
10.1101/gr.136598.111
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发表时间：
2012-08
期刊：
影响因子：
7
通讯作者：
Saffery R
中科院分区：
文献类型：
--
作者：
Gordon L;Joo JE;Powell JE;Ollikainen M;Novakovic B;Li X;Andronikos R;Cruickshank MN;Conneely KN;Smith AK;Alisch RS;Morley R;Visscher PM;Craig JM;Saffery R
单卵（MZ）和双卵（DZ）双胞胎组之间的比较，使遗传和共享和非共享的环境因素表型变异的相对贡献的估计。使用20,000个CpG位点的DNA甲基化谱作为表型，我们检测了来自22对MZ和12对DZ双胞胎的三种新生儿组织中的不一致水平。MZ双胞胎在出生时表现出广泛的对内差异，但表现出的不一致性水平通常低于DZ对。在所有双胞胎中，CpG岛的对内甲基化不一致性最低，并随着与岛屿的距离而增加。方差分量分解分析的DNA甲基化的MZ和DZ对揭示了低的平均遗传力在所有组织中，虽然检测到广泛的遗传力特定的基因组CpG位点。变化的最大组成部分是由于非共享宫内环境和随机因素的综合影响。甲基化对出生体重的回归分析揭示了参与代谢和生物合成的基因甲基化之间的一般关联，为先前描述的低出生体重与心血管、代谢和其他复杂疾病风险增加之间的联系的表观遗传变化提供了进一步的支持。最后，将我们的数据与几个年长双胞胎的数据进行比较，发现几乎没有证据表明全基因组表观遗传漂移随年龄的增加而增加。这是第一项在双胞胎出生时在基因组规模上分析DNA甲基化的研究，进一步强调了宫内环境对塑造新生儿表观基因组的重要性。
Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ∼20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.
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影响因子：
3.7
作者：
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
通讯作者：
Ophoff RA
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
影响因子：
64.5
作者：
Altschuler SJ;Wu LF
通讯作者：
Wu LF
影响因子：
14.9
作者：
Bock C;Walter J;Paulsen M;Lengauer T
通讯作者：
Lengauer T