Stephanie Shiau1, Leishen Wang2, Huikun Liu2, Yinan Zheng3, Alex Drong4, Brian T Joyce3, Jun Wang3, Weiqin Li2, Junhong Leng2, Yun Shen5, Ru Gao5, Gang Hu5, Lifang Hou3, Andrea A Baccarelli4. 1. Department of Biostatistics and Epidemiology, Rutgers School of Public Health , Piscataway, NJ, USA. 2. Tianjin Women's and Children's Health Center , Tianjin, China. 3. Center for Global Oncology, Institute for Global Health, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University , Chicago, IL, USA. 4. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University , New York, NY, USA. 5. Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center , Baton Rouge, LA, USA.
Abstract
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 an exam with anthropometric measurements and blood draw for DNAm analysis (Illumina 850 K 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 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). Increased offspring DNAm age acceleration 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 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.
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 an exam with anthropometric measurements and blood draw for DNAm analysis (Illumina 850 K 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 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). Increased offspring DNAm age acceleration 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 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.
Entities:
Keywords:
DNA methylation; Gestational diabetes mellitus; epigenetic age
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