DNA methylation age at birth and childhood: performance of epigenetic clocks and characteristics associated with epigenetic age acceleration in the Project Viva cohort.
Anne K Bozack, Sheryl L Rifas-Shiman, Diane R Gold, Zachary M Laubach, Wei Perng, Marie-France Hivert, Andres Cardenas
{"title":"DNA methylation age at birth and childhood: performance of epigenetic clocks and characteristics associated with epigenetic age acceleration in the Project Viva cohort.","authors":"Anne K Bozack, Sheryl L Rifas-Shiman, Diane R Gold, Zachary M Laubach, Wei Perng, Marie-France Hivert, Andres Cardenas","doi":"10.1186/s13148-023-01480-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099681/pdf/","citationCount":"6","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Epigenetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13148-023-01480-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
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.
Clinical EpigeneticsBiochemistry, 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.