TY - JOUR
T1 - Prenatal gestational diabetes mellitus exposure and accelerated offspring DNA methylation age in early childhood
AU - Shiau, Stephanie
AU - Wang, Leishen
AU - Liu, Huikun
AU - Zheng, Yinan
AU - Drong, Alex
AU - Joyce, Brian T.
AU - Wang, Jun
AU - Li, Weiqin
AU - Leng, Junhong
AU - Shen, Yun
AU - Gao, Ru
AU - Hu, Gang
AU - Hou, Lifang
AU - Baccarelli, Andrea A.
N1 - Funding Information:
This study was supported by grants from the European Foundation for the Study of Diabetes (EFSD)/Chinese Diabetes Society (CDS)/Lilly programme for Collaborative Research between China and Europe, and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100790). This project also used core facilities supported by the NORC Center Grant P30 DK072476, and the COBRE Center Grant P30 GM118430. Dr. Hu was partly supported by the grant from the National Institute of General Medical Sciences (U54GM104940). Dr. Baccarelli was partially supported by a grant from the National Institute of Environmental Health Studies (P30ES009089). Dr. Hou was partially supported by the American Heart Association Children’s Strategically Focused Research Network.
Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020
Y1 - 2020
N2 - Background: We investigated the association between prenatal GDM exposure and offspring DNA methylation (DNAm) age at 3-10 years of age in the Tianjin GDM Observational Study. Methods: This study included 578 GDM and 578 non-GDM mother-child pairs. Children underwent a physical exam that included anthropometric measurements and a blood draw for DNAm analysis (Illumina 850K array) at a median age of 5.9 years (range 3.1-10.2). DNAm age was calculated using two epigenetic clock algorithms (Horvath and Hannum). The residual resulting from regressing DNAm age on chronological age was used as a metric for age acceleration. Results: Chronological age was positively correlated with Horvath DNAm age (r=0.53,p<0.0001) and Hannum DNAm age (r=0.38,p<0.0001). Offspring age acceleration was higher in the GDM group than the non-GDM group after adjustment for potential confounders (Horvath: 4.96 months higher, adjusted for sex, pre-pregnancy BMI, cell-type proportions, and technical bias,p=0.0002; Hannum: 11.2 months higher, adjusted for cell-type proportions and technical bias,p<0.0001). Adjusted for age, sex, and pre-pregnancy BMI, increased offspring DNAm age acceleration by both methods was associated with increased offspring weight-for-age Z-score, BMI-for-age-Z-score, waist circumference, body fat percentage, subscapular skinfold, suprailiac skinfold, upper-arm circumference, and blood pressure; findings were stronger in the GDM group. Conclusions: We found that offspring of women with GDM exhibit accelerated epigenetic age compared to control participants, independent of other maternal factors. Epigenetic age in offspring was also associated with cardiometabolic risk factors, suggesting that GDM and GDM-associated factors may have long-term effects on offspring epigenetic age and contribute to health outcomes.
AB - Background: We investigated the association between prenatal GDM exposure and offspring DNA methylation (DNAm) age at 3-10 years of age in the Tianjin GDM Observational Study. Methods: This study included 578 GDM and 578 non-GDM mother-child pairs. Children underwent a physical exam that included anthropometric measurements and a blood draw for DNAm analysis (Illumina 850K array) at a median age of 5.9 years (range 3.1-10.2). DNAm age was calculated using two epigenetic clock algorithms (Horvath and Hannum). The residual resulting from regressing DNAm age on chronological age was used as a metric for age acceleration. Results: Chronological age was positively correlated with Horvath DNAm age (r=0.53,p<0.0001) and Hannum DNAm age (r=0.38,p<0.0001). Offspring age acceleration was higher in the GDM group than the non-GDM group after adjustment for potential confounders (Horvath: 4.96 months higher, adjusted for sex, pre-pregnancy BMI, cell-type proportions, and technical bias,p=0.0002; Hannum: 11.2 months higher, adjusted for cell-type proportions and technical bias,p<0.0001). Adjusted for age, sex, and pre-pregnancy BMI, increased offspring DNAm age acceleration by both methods was associated with increased offspring weight-for-age Z-score, BMI-for-age-Z-score, waist circumference, body fat percentage, subscapular skinfold, suprailiac skinfold, upper-arm circumference, and blood pressure; findings were stronger in the GDM group. Conclusions: We found that offspring of women with GDM exhibit accelerated epigenetic age compared to control participants, independent of other maternal factors. Epigenetic age in offspring was also associated with cardiometabolic risk factors, suggesting that GDM and GDM-associated factors may have long-term effects on offspring epigenetic age and contribute to health outcomes.
KW - DNA methylation
KW - Gestational diabetes mellitus
KW - epigenetic age
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U2 - 10.1080/15592294.2020.1790924
DO - 10.1080/15592294.2020.1790924
M3 - Article
C2 - 32614694
AN - SCOPUS:85087773479
SN - 1559-2294
SP - 1
EP - 10
JO - Epigenetics
JF - Epigenetics
ER -