Reproduction, DNA methylation and biological age

Reproduction, DNA methylation and biological age
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DOI:
10.1093/humrep/dez149
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发表时间:
2019-10-01
期刊:
影响因子:
6.1
通讯作者:
Taylor, Jack A.
Taylor, Jack A.
中科院分区:
医学1区
文献类型:
--
作者:
Kresovich, Acob K.;Harmon, Quaker E.;Taylor, Jack A.

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研究问题:生殖特征是否与全基因组DNA甲基化和表观遗传年龄有关?总结答案:我们的数据表明,生育能力的提高与血液DNA甲基化的差异和表观遗传年龄的小幅增加有关。已知的是:一项对397名年轻菲律宾妇女(20-22岁)的研究观察到,表观遗传年龄随着怀孕次数的增加而增加。研究设计、大小、持续时间:我们使用了2356名非西班牙裔白人妇女(年龄35-74岁)的数据,这些数据登记在SISTER研究队列中。在2356名妇女中,1897名(81%)报告至少有一名活产。在临产妇女中,487名(26%)妇女报告曾经历过妊娠并发症。三个表观遗传学时钟(即Hannum、Horvath和Levine)和全基因组的甲基化被使用Illumina的HumanMethylation450珠芯片在全血DNA中进行了测量。我们使用线性回归估计了关联fl值和95%的CI。MAIN结果和机率的作用:所有三个表观遗传Dack显示出生数量和表观遗传年龄之间的弱关联(每个活着出生;Hannum:Beta=0.16,95%CI=0.02,0.29,P=0.03;Horvath:Beta=0.12,95%CI=-0.04,0.27,P=0.14;Levine:Beta=0.27,95%CI=0.08,0.45,P=0.01);然而,对当前BMI的额外调整减弱了这种关联。在临产妇女中,孕期糖耐量异常与Hannum时钟(β=0.96;95%CI=0.10,1.81;P=0.03)和Levine时钟(β=1.69;95%CI=0.54,2.84;P<0.01)的表观遗传年龄增加有关。在表观基因组分析中,产次增加与17个CpG位点的甲基化差异有关(Bonferroni校正P
STUDY QUESTION: Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age?SUMMARY ANSWER: Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age.WHAT IS KNOWN ALREADY: A study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies.STUDY DESIGN, SIZE, DURATION: We used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort.PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina's HumanMethylation450 BeadChip. We estimated association fl-values and 95% Cis using linear regression.MAIN RESULTS AND THE ROLE OF CHANCE: All three epigenetic docks showed weak associations between number of births and epigenetic age (per live birth; Hannum: beta = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: beta = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine:beta = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (beta = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (beta = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P