Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans.
Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans.
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DOI：
10.1038/s41598-024-52433-5
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发表时间：
2024-01-23
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
关于产前可卡因暴露（PCE）对后代影响的调查并不一致，很少有研究调查人类的生物学结果。我们分析了有（n = 35）和没有（n = 47）PCE的新生儿脐带血（UCB）的全基因组DNA甲基化（DNAm）。我们使用 DNAm 数据 (1) 评估出生时的儿科表观遗传时钟，以及 (2) 估计终生疾病的表观遗传评分 (ES)。我们根据 Knight 和 Bohlin 表观遗传时钟生成了妊娠表观遗传年龄估计 (DNAmGA)。我们还研究了 DNAmGA 和 UCB 血清脑源性神经营养因子 (BDNF) 水平之间的关联。考虑到大规模 DNAm 数据的可用性和现有证据表明 PCE 是晚年健康问题的风险，我们生成了吸烟、精神病、自闭症、糖尿病和肥胖的 ES。对 ES 中包含的具有组间差异的 CpG 进行基因本体 (GO) 分析。 PCE 与新生儿 DNAmGA 较低有关，并且在控制潜在混杂因素（例如通过 DNAm 和产科数据预测的血细胞类型组成）时，这种效应仍然显着。 DNAmGA与UCB血清中BDNF水平呈负相关。 PCE 组中吸烟、精神病和糖尿病 ES 的发生率较高。 GO 分析揭示 GABA 能突触是 PCE 改变的潜在途径。我们对与 PCE 相关的不良表型的 DNAmGA 和 ES 减速的研究结果表明，妊娠期可卡因暴露对人类新生儿表观遗传景观的影响在出生时就可以检测到。
The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale DNAm data availability and existing evidence regarding PCE as a risk for health problems later in life, we generated ES for tobacco smoking, psychosis, autism, diabetes, and obesity. A gene ontology (GO) analysis on the CpGs included in the ES with group differences was performed. PCE was associated with lower DNAmGA in newborns, and this effect remained significant when controlling for potential confounders, such as blood cell type composition predicted by DNAm and obstetric data. DNAmGA was negatively correlated with BDNF levels in the serum of UCB. Higher tobacco smoking, psychosis, and diabetes ES were found in the PCE group. The GO analysis revealed GABAergic synapses as a potential pathway altered by PCE. Our findings of decelerated DNAmGA and ES for adverse phenotypes associated with PCE, suggest that the effects of gestational cocaine exposure on the epigenetic landscape of human newborns are detectable at birth.
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影响因子：
5.7
作者：
Haftorn KL;Lee Y;Denault WRP;Page CM;Nustad HE;Lyle R;Gjessing HK;Malmberg A;Magnus MC;Næss Ø;Czamara D;Räikkönen K;Lahti J;Magnus P;Håberg SE;Jugessur A;Bohlin J
通讯作者：
Bohlin J
血液DNA甲基化和自闭症谱系障碍的病例对照荟萃分析。
影响因子：
6.2
作者：
Andrews SV;Sheppard B;Windham GC;Schieve LA;Schendel DE;Croen LA;Chopra P;Alisch RS;Newschaffer CJ;Warren ST;Feinberg AP;Fallin MD;Ladd-Acosta C
通讯作者：
Ladd-Acosta C
影响因子：
7.7
作者：
Hannon E;Dempster EL;Mansell G;Burrage J;Bass N;Bohlken MM;Corvin A;Curtis CJ;Dempster D;Di Forti M;Dinan TG;Donohoe G;Gaughran F;Gill M;Gillespie A;Gunasinghe C;Hulshoff HE;Hultman CM;Johansson V;Kahn RS;Kaprio J;Kenis G;Kowalec K;MacCabe J;McDonald C;McQuillin A;Morris DW;Murphy KC;Mustard CJ;Nenadic I;O'Donovan MC;Quattrone D;Richards AL;Rutten BP;St Clair D;Therman S;Toulopoulou T;Van Os J;Waddington JL;Wellcome Trust Case Control Consortium (WTCCC);CRESTAR consortium;Sullivan P;Vassos E;Breen G;Collier DA;Murray RM;Schalkwyk LS;Mill J
通讯作者：
Mill J
影响因子：
8.2
作者：
Fraszczyk E;Spijkerman AMW;Zhang Y;Brandmaier S;Day FR;Zhou L;Wackers P;Dollé MET;Bloks VW;Gào X;Gieger C;Kooner J;Kriebel J;Picavet HSJ;Rathmann W;Schöttker B;Loh M;Verschuren WMM;van Vliet-Ostaptchouk JV;Wareham NJ;Chambers JC;Ong KK;Grallert H;Brenner H;Luijten M;Snieder H
通讯作者：
Snieder H
影响因子：
2.3
作者：
Lee, Chun-Ting;Chen, Jia;Worden, Lila T.;Freed, William J.
通讯作者：
Freed, William J.