DNA methylation age at birth and childhood: performance of epigenetic clocks and characteristics associated with epigenetic age acceleration in the Project Viva cohort.

IF 5.7 2区 医学 Q1 Medicine Clinical Epigenetics Pub Date : 2023-04-12 DOI:10.1186/s13148-023-01480-2
Anne K Bozack, Sheryl L Rifas-Shiman, Diane R Gold, Zachary M Laubach, Wei Perng, Marie-France Hivert, Andres Cardenas
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引用次数: 6

Abstract

Background: Epigenetic age acceleration (EAA) and epigenetic gestational age acceleration (EGAA) are biomarkers of physiological development and may be affected by the perinatal environment. The aim of this study was to evaluate performance of epigenetic clocks and to identify biological and sociodemographic correlates of EGAA and EAA at birth and in childhood. In the Project Viva pre-birth cohort, DNA methylation was measured in nucleated cells in cord blood (leukocytes and nucleated red blood cells, N = 485) and leukocytes in early (N = 120, median age = 3.2 years) and mid-childhood (N = 460, median age = 7.7 years). We calculated epigenetic gestational age (EGA; Bohlin and Knight clocks) and epigenetic age (EA; Horvath and skin & blood clocks), and respective measures of EGAA and EAA. We evaluated the performance of clocks relative to chronological age using correlations and median absolute error. We tested for associations of maternal-child characteristics with EGAA and EAA using mutually adjusted linear models controlling for estimated cell type proportions. We also tested associations of Horvath EA at birth with childhood EAA.

Results: Bohlin EGA was strongly correlated with chronological gestational age (Bohlin EGA r = 0.82, p < 0.001). Horvath and skin & blood EA were weakly correlated with gestational age, but moderately correlated with chronological age in childhood (r = 0.45-0.65). Maternal smoking during pregnancy was associated with higher skin & blood EAA at birth [B (95% CI) = 1.17 weeks (- 0.09, 2.42)] and in early childhood [0.34 years (0.03, 0.64)]. Female newborns and children had lower Bohlin EGAA [- 0.17 weeks (- 0.30, - 0.04)] and Horvath EAA at birth [B (95% CI) = - 2.88 weeks (- 4.41, - 1.35)] and in childhood [early childhood: - 0.3 years (- 0.60, 0.01); mid-childhood: - 0.48 years (- 0.77, - 0.18)] than males. When comparing self-reported Asian, Black, Hispanic, and more than one race or other racial/ethnic groups to White, we identified significant differences in EGAA and EAA at birth and in mid-childhood, but associations varied across clocks. Horvath EA at birth was positively associated with childhood Horvath and skin & blood EAA.

Conclusions: Maternal smoking during pregnancy and child sex were associated with EGAA and EAA at multiple timepoints. Further research may provide insight into the relationship between perinatal factors, pediatric epigenetic aging, and health and development across the lifespan.

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出生和童年时的DNA甲基化年龄:Viva项目队列中表观遗传时钟的表现和与表观遗传年龄加速相关的特征。
背景:表观遗传年龄加速(EAA)和表观遗传胎龄加速(EGAA)是生理发育的生物标志物,可能受到围产期环境的影响。本研究的目的是评估表观遗传时钟的表现,并确定EGAA和EAA在出生和童年时期的生物学和社会人口学相关性。在Viva项目出生前队列中,在脐带血(白细胞和有核红细胞,N = 485)和早期(N = 120,中位年龄= 3.2岁)和童年中期(N = 460,中位年龄= 7.7岁)的有核细胞中测量DNA甲基化。我们计算了表观遗传胎龄(EGA;Bohlin和Knight时钟)和表观遗传年龄(EA;Horvath和皮肤和血液时钟),以及EGAA和EAA的各自测量。我们使用相关性和中位数绝对误差来评估时钟相对于实足年龄的性能。我们使用相互调整的线性模型控制估计的细胞类型比例,测试了母子特征与EGAA和EAA的关联。我们还测试了出生时Horvath EA与儿童期EAA的关系。结果:Bohlin EGA与实足胎龄密切相关(Bohlin EGA r = 0.82, p)。结论:孕期吸烟和儿童性行为与EGAA和EAA在多个时间点存在相关性。进一步的研究可能会为围产期因素、儿童表观遗传衰老与整个生命周期的健康和发育之间的关系提供深入的见解。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
期刊最新文献
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