Sex differences of leukocytes DNA methylation adjusted for estimated cellular proportions.
Sex differences of leukocytes DNA methylation adjusted for estimated cellular proportions.
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白细胞的性别差异DNA甲基化调整了估计的细胞比例。
DOI：
10.1186/s13293-015-0029-7
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发表时间：
2015
影响因子：
7.9
通讯作者：
Ohmori T
中科院分区：
文献类型：
--
作者：
Inoshita M;Numata S;Tajima A;Kinoshita M;Umehara H;Yamamori H;Hashimoto R;Imoto I;Ohmori T
DNA甲基化，最常见的是甲基转移到CpG二核苷酸中胞嘧啶的5碳位置，在正常发育和疾病中都起着重要作用。迄今为止，一些全基因组甲基化研究已经揭示了性别偏倚的DNA甲基化，但没有研究通过考虑细胞异质性来调查DNA甲基化的性别差异。本研究的目的是通过调整估计的细胞比例来研究人类血液中常染色体上的性别偏倚DNA甲基化，因为细胞类型比例可能因性别而异。我们使用Infinium HumanMethylation450 BeadChips对两组样本进行了全基因组DNA甲基化分析，一组是发现组（49名男性和44名女性），另一组是复制组（14名男性和10名女性），检测485,764个CpG二核苷酸，然后在调整年龄、估计的6种细胞类型比例和代理变量分析中确定的共变量后，使用多元线性回归分析检查性别对DNA甲基化的影响。我们在发现集中发现了292个常染色体CpG位点的男性和女性DNA甲基化差异（bonferroni校正p < 0.05）。在292个CpG位点中，98个位点存在显著性差异（p < 0.05）。这些发现进一步证明了DNA甲基化可能在两性二态性的分化或维持中发挥作用。我们对性别影响的甲基组图谱可能有助于理解正常发育和疾病的分子机制。本文的在线版本（doi:10.1186/s13293-015-0029-7）包含补充材料，仅供授权用户使用。
DNA methylation, which is most frequently the transference of a methyl group to the 5-carbon position of the cytosine in a CpG dinucleotide, plays an important role in both normal development and diseases. To date, several genome-wide methylome studies have revealed sex-biased DNA methylation, yet no studies have investigated sex differences in DNA methylation by taking into account cellular heterogeneity. The aim of the present study was to investigate sex-biased DNA methylation on the autosomes in human blood by adjusting for estimated cellular proportions because cell-type proportions may vary by sex. We performed a genome-wide DNA methylation profiling of the peripheral leukocytes in two sets of samples, a discovery set (49 males and 44 females) and a replication set (14 males and 10 females) using Infinium HumanMethylation450 BeadChips for 485,764 CpG dinucleotides and then examined the effect of sex on DNA methylation with a multiple linear regression analysis after adjusting for age, the estimated 6 cell-type proportions, and the covariates identified in a surrogate variable analysis. We identified differential DNA methylation between males and females at 292 autosomal CpG site loci in the discovery set (Bonferroni-adjusted p < 0.05). Of these 292 CpG sites, significant sex differences were also observed at 98 sites in the replication set (p < 0.05). These findings provided further evidence that DNA methylation may play a role in the differentiation or maintenance of sexual dimorphisms. Our methylome mapping of the effects of sex may be useful to understanding the molecular mechanism involved in both normal development and diseases. The online version of this article (doi:10.1186/s13293-015-0029-7) contains supplementary material, which is available to authorized users.
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影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
3.7
作者：
Liu J;Morgan M;Hutchison K;Calhoun VD
通讯作者：
Calhoun VD
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3.8
作者：
Dedeurwaerder, Sarah;Defrance, Matthieu;Fuks, Francois
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Fuks, Francois
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：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard