Cord blood DNA methylation and adiposity measures in early and mid-childhood
Abstract Background Excess adiposity in childhood is associated with numerous adverse health outcomes. As this condition is difficult to treat once present, identification of risk early in life can help inform and implement strategies to prevent the onset of the condition. We performed an epigenome-...
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doaj-703ea8bd4b5343bab9473420b361b21e2020-11-25T00:44:00ZengBMCClinical Epigenetics1868-70751868-70832017-08-01911910.1186/s13148-017-0384-9Cord blood DNA methylation and adiposity measures in early and mid-childhoodJacob K. Kresovich0Yinan Zheng1Andres Cardenas2Brian T. Joyce3Sheryl L. Rifas-Shiman4Emily Oken5Matthew W. Gillman6Marie-France Hivert7Andrea A. Baccarelli8Lifang Hou9Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at ChicagoCenter for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern UniversityDivision of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteCenter for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern UniversityDivision of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteDivision of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteEnvironmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of HealthDivision of Chronic Disease Research Across the Lifecourse (CoRAL), Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteDepartment of Environmental Health Science, Mailman School of Public Health, Columbia UniversityCenter for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern UniversityAbstract Background Excess adiposity in childhood is associated with numerous adverse health outcomes. As this condition is difficult to treat once present, identification of risk early in life can help inform and implement strategies to prevent the onset of the condition. We performed an epigenome-wide association study to prospectively investigate the relationship between cord blood DNA methylation and adiposity measurements in childhood. Methods We measured genome-wide DNA methylation from 478 children in cord blood and measured overall and central adiposity via skinfold caliper measurements in early (range 3.1–3.3 years) and mid-childhood (age range 7.3–8.3 years) and via dual X-ray absorptiometry (DXA) in mid-childhood. Final models were adjusted for maternal age at enrollment, pre-pregnancy body mass index, education, folate intake during pregnancy, smoking during pregnancy, and gestational weight gain, and child sex, race/ethnicity, current age, and cord blood cell composition. Results We identified four promoter proximal CpG sites that were associated with adiposity as measured by subscapular (SS) and triceps (TR) ratio (SS:TR) in early childhood, in the genes KPRP, SCL9A10, MYLK2, and PRLHR. We additionally identified one gene body CpG site associated with early childhood SS + TR on PPAPDC1A; this site was nominally associated with SS + TR in mid-childhood. Higher methylation at one promoter proximal CpG site in MMP25 was also associated with SS:TR in mid-childhood. In regional analyses, methylation at an exonal region of GFPT2 was positively associated with SS:TR in early childhood. Finally, we identified regions of two long, non-coding RNAs which were associated with SS:TR (LOC100049716) and fat-free mass index (LOC102723493) in mid-childhood. Conclusion This analysis identified novel CpG loci associated with adiposity outcomes. However, our results suggest little consistency across the various adiposity outcomes tested, particularly among the more accurate DXA measurements of body composition. We recommend using caution when interpreting these associations.http://link.springer.com/article/10.1186/s13148-017-0384-9EWASCord bloodMethylationAdiposityChildhood adiposity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jacob K. Kresovich Yinan Zheng Andres Cardenas Brian T. Joyce Sheryl L. Rifas-Shiman Emily Oken Matthew W. Gillman Marie-France Hivert Andrea A. Baccarelli Lifang Hou |
spellingShingle |
Jacob K. Kresovich Yinan Zheng Andres Cardenas Brian T. Joyce Sheryl L. Rifas-Shiman Emily Oken Matthew W. Gillman Marie-France Hivert Andrea A. Baccarelli Lifang Hou Cord blood DNA methylation and adiposity measures in early and mid-childhood Clinical Epigenetics EWAS Cord blood Methylation Adiposity Childhood adiposity |
author_facet |
Jacob K. Kresovich Yinan Zheng Andres Cardenas Brian T. Joyce Sheryl L. Rifas-Shiman Emily Oken Matthew W. Gillman Marie-France Hivert Andrea A. Baccarelli Lifang Hou |
author_sort |
Jacob K. Kresovich |
title |
Cord blood DNA methylation and adiposity measures in early and mid-childhood |
title_short |
Cord blood DNA methylation and adiposity measures in early and mid-childhood |
title_full |
Cord blood DNA methylation and adiposity measures in early and mid-childhood |
title_fullStr |
Cord blood DNA methylation and adiposity measures in early and mid-childhood |
title_full_unstemmed |
Cord blood DNA methylation and adiposity measures in early and mid-childhood |
title_sort |
cord blood dna methylation and adiposity measures in early and mid-childhood |
publisher |
BMC |
series |
Clinical Epigenetics |
issn |
1868-7075 1868-7083 |
publishDate |
2017-08-01 |
description |
Abstract Background Excess adiposity in childhood is associated with numerous adverse health outcomes. As this condition is difficult to treat once present, identification of risk early in life can help inform and implement strategies to prevent the onset of the condition. We performed an epigenome-wide association study to prospectively investigate the relationship between cord blood DNA methylation and adiposity measurements in childhood. Methods We measured genome-wide DNA methylation from 478 children in cord blood and measured overall and central adiposity via skinfold caliper measurements in early (range 3.1–3.3 years) and mid-childhood (age range 7.3–8.3 years) and via dual X-ray absorptiometry (DXA) in mid-childhood. Final models were adjusted for maternal age at enrollment, pre-pregnancy body mass index, education, folate intake during pregnancy, smoking during pregnancy, and gestational weight gain, and child sex, race/ethnicity, current age, and cord blood cell composition. Results We identified four promoter proximal CpG sites that were associated with adiposity as measured by subscapular (SS) and triceps (TR) ratio (SS:TR) in early childhood, in the genes KPRP, SCL9A10, MYLK2, and PRLHR. We additionally identified one gene body CpG site associated with early childhood SS + TR on PPAPDC1A; this site was nominally associated with SS + TR in mid-childhood. Higher methylation at one promoter proximal CpG site in MMP25 was also associated with SS:TR in mid-childhood. In regional analyses, methylation at an exonal region of GFPT2 was positively associated with SS:TR in early childhood. Finally, we identified regions of two long, non-coding RNAs which were associated with SS:TR (LOC100049716) and fat-free mass index (LOC102723493) in mid-childhood. Conclusion This analysis identified novel CpG loci associated with adiposity outcomes. However, our results suggest little consistency across the various adiposity outcomes tested, particularly among the more accurate DXA measurements of body composition. We recommend using caution when interpreting these associations. |
topic |
EWAS Cord blood Methylation Adiposity Childhood adiposity |
url |
http://link.springer.com/article/10.1186/s13148-017-0384-9 |
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