TY - JOUR
T1 - Cord blood DNA methylation and adiposity measures in early and mid-childhood
AU - Kresovich, Jacob K.
AU - Zheng, Yinan
AU - Cardenas, Andres
AU - Joyce, Brian T.
AU - Rifas-Shiman, Sheryl L.
AU - Oken, Emily
AU - Gillman, Matthew W.
AU - Hivert, Marie France
AU - Baccarelli, Andrea A.
AU - Hou, Lifang
N1 - Funding Information:
We would like to thank the staff and participants of Project Viva. The views expressed in this article do not necessarily represent the views of the US Government, the Department of Health and Human Services, or the National Institutes of Health. Funding Project Viva is supported by the grants from the NIH (R01 HD 034568, K24 HD069408, R01 NR013945, UG3 OD023286). This work was additionally funded by the National Cancer Institute (R25 CA057699).
PY - 2017/8/15
Y1 - 2017/8/15
N2 - 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.
AB - 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.
KW - Adiposity
KW - Childhood adiposity
KW - Cord blood
KW - EWAS
KW - Methylation
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U2 - 10.1186/s13148-017-0384-9
DO - 10.1186/s13148-017-0384-9
M3 - Article
C2 - 28814982
AN - SCOPUS:85027500801
VL - 9
JO - Clinical Epigenetics
JF - Clinical Epigenetics
SN - 1868-7075
IS - 1
M1 - 86
ER -