Longitudinal analysis of DNA methylation associated with birth weight and gestational age.
Longitudinal analysis of DNA methylation associated with birth weight and gestational age.
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DOI：
10.1093/hmg/ddv119
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发表时间：
2015-07-01
影响因子：
3.5
通讯作者：
Relton CL
中科院分区：
文献类型：
--
作者：
Simpkin AJ;Suderman M;Gaunt TR;Lyttleton O;McArdle WL;Ring SM;Tilling K;Davey Smith G;Relton CL
胎龄(GA)和出生体重被认为是决定长期健康的关键因素。有人假设，DNA甲基化的变化可能会介导这些长期影响。我们从雅芳父母和儿童纵向研究中获得了7岁和17岁同一儿童脐带血和外周血的DNA甲基化图谱。重复测量数据被用来调查儿童和青春期出生相关甲基化的变化。分析了10种发育表型(如身高)，以确定DNA甲基化对健康影响的可能中介作用。在脐带血中，发现224个CpG位点的甲基化与GA相关，23个CpG位点的甲基化与出生体重相关。随着时间的推移，这些位点中的大多数发生了甲基化变化，但这两个出生特征都与7岁或17岁时的甲基化没有很强的关联(使用保守的校正P<；1.03×10-7多次测试)，这表明差异甲基化在儿童早期就解决了。观察到与出生体重相关的CpG位点与儿童时期的表型特征之间存在关联。一个很强的关联涉及出生体重、NFIX基因近端CpG位点的甲基化和17岁时的骨密度。对出生到青春期的系列甲基化分析提供了证据，证明在儿童早期缺乏持续的甲基化差异。与出生体重相关的位置与发育基因有关，并具有与发育表型相关的甲基化水平。需要复制和询问因果关系，以证实出生时甲基化差异是否影响出生体重和发育之间的联系。
Gestational age (GA) and birth weight have been implicated in the determination of long-term health. It has been hypothesized that changes in DNA methylation may mediate these long-term effects. We obtained DNA methylation profiles from cord blood and peripheral blood at ages 7 and 17 in the same children from the Avon Longitudinal Study of Parents and Children. Repeated-measures data were used to investigate changes in birth-related methylation during childhood and adolescence. Ten developmental phenotypes (e.g. height) were analysed to identify possible mediation of health effects by DNA methylation. In cord blood, methylation at 224 CpG sites was found to be associated with GA and 23 CpG sites with birth weight. Methylation changed in the majority of these sites over time, but neither birth characteristic was strongly associated with methylation at age 7 or 17 (using a conservative correction for multiple testing of P < 1.03 × 10–7), suggesting resolution of differential methylation by early childhood. Associations were observed between birth weight-associated CpG sites and phenotypic characteristics in childhood. One strong association involved birth weight, methylation of a CpG site proximal to the NFIX locus and bone mineral density at age 17. Analysis of serial methylation from birth to adolescence provided evidence for a lack of persistence of methylation differences beyond early childhood. Sites associated with birth weight were linked to developmental genes and have methylation levels which are associated with developmental phenotypes. Replication and interrogation of causal relationships are needed to substantiate whether methylation differences at birth influence the association between birth weight and development.
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全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
3.8
作者：
Dedeurwaerder, Sarah;Defrance, Matthieu;Fuks, Francois
通讯作者：
Fuks, Francois
影响因子：
4.2
作者：
Harvey, Nicholas C.;Lillycrop, Karen A.;Cooper, Cyrus
通讯作者：
Cooper, Cyrus
影响因子：
12.3
作者：
Cruickshank MN;Oshlack A;Theda C;Davis PG;Martino D;Sheehan P;Dai Y;Saffery R;Doyle LW;Craig JM
通讯作者：
Craig JM
影响因子：
3.7
作者：
Herbstman, Julie B.;Wang, Shuang;Tang, Deliang
通讯作者：
Tang, Deliang