Yoon-Jung Choi1, Young Ah Lee2, Yun-Chul Hong3, Jinwoo Cho4, Kyung-Shin Lee1, Choong Ho Shin2, Bung-Nyun Kim5, Johanna Inhyang Kim6, Soo Jin Park7, Hans Bisgaard8, Klaus Bønnelykke8, Youn-Hee Lim9. 1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Environmental Health Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. 2. Department of Pediatrics, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. 3. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Environmental Health Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea. 4. Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea. 5. Division of Children and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital, Seoul 03080, Republic of Korea. 6. Department of Psychiatry, Hanyang University Medical Center, Seoul 04763, Republic of Korea. 7. Department of Surgery, Wonkwang University Sanbon Hospital, Gunpo 15865, Republic of Korea. 8. COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen, 2820, Gentofte, Copenhagen, Denmark. 9. Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea; Section of Environmental Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen 1014, Denmark. Electronic address: younhee.lim@sund.ku.dk.
Abstract
OBJECTIVES: Epigenetic mechanisms have been suggested to play a role in the link between in utero exposure to bisphenol A (BPA) and pediatric obesity; however, there is little evidence regarding this mechanism in humans. We obtained data on obesity-associated CpG sites from a previous epigenome-wide association study, and then examined whether methylation at those CpG sites was influenced by prenatal BPA exposure. We then evaluated the relationship between CpG methylation status and body mass index (BMI) in a prospective children's cohort at ages 2, 4, 6, and 8 years. METHODS: Methylation profiles of 59 children were longitudinally analyzed at ages 2 and 6 years using the Infinium Human Methylation BeadChip. A total of 594 CpG sites known to be BMI or obesity-associated sites were tested for an association with prenatal BPA levels, categorized into low and high exposure groups based on the 80th percentile of maternal BPA levels (2.68 μg/g creatinine), followed by an analysis of the association between DNA methylation and BMI from ages 2-8. RESULTS: There was a significant increase in the methylation levels of cg19196862 (IGF2R) in the high BPA group at age 2 years (p = 0.00030, false discovery rate corrected p < 0.10) but not at age 6. With one standard deviation increase of methylation at cg19196862 (IGF2R) at age 2 years, the linear mixed model analysis revealed that BMI during ages 2-8 years significantly increased by 0.49 (95% confidence interval; 0.08, 0.90) in girls, but not in boys. The indirect effect of prenatal BPA exposure on early childhood BMI through methylation at cg19196862 (IGF2R) at age 2 years was marginally significant. CONCLUSIONS: Prenatal exposure to BPA may influence differential methylation of IGF2R at age 2. This result indicates that a possible sensitive period of DNA methylation occurs earlier during development, which may affect BMI until later childhood in a sex-specific manner.
OBJECTIVES: Epigenetic mechanisms have been suggested to play a role in the link between in utero exposure to bisphenol A (BPA) and pediatric obesity; however, there is little evidence regarding this mechanism in humans. We obtained data on obesity-associated CpG sites from a previous epigenome-wide association study, and then examined whether methylation at those CpG sites was influenced by prenatal BPA exposure. We then evaluated the relationship between CpG methylation status and body mass index (BMI) in a prospective children's cohort at ages 2, 4, 6, and 8 years. METHODS: Methylation profiles of 59 children were longitudinally analyzed at ages 2 and 6 years using the Infinium Human Methylation BeadChip. A total of 594 CpG sites known to be BMI or obesity-associated sites were tested for an association with prenatal BPA levels, categorized into low and high exposure groups based on the 80th percentile of maternal BPA levels (2.68 μg/g creatinine), followed by an analysis of the association between DNA methylation and BMI from ages 2-8. RESULTS: There was a significant increase in the methylation levels of cg19196862 (IGF2R) in the high BPA group at age 2 years (p = 0.00030, false discovery rate corrected p < 0.10) but not at age 6. With one standard deviation increase of methylation at cg19196862 (IGF2R) at age 2 years, the linear mixed model analysis revealed that BMI during ages 2-8 years significantly increased by 0.49 (95% confidence interval; 0.08, 0.90) in girls, but not in boys. The indirect effect of prenatal BPA exposure on early childhood BMI through methylation at cg19196862 (IGF2R) at age 2 years was marginally significant. CONCLUSIONS: Prenatal exposure to BPA may influence differential methylation of IGF2R at age 2. This result indicates that a possible sensitive period of DNA methylation occurs earlier during development, which may affect BMI until later childhood in a sex-specific manner.
Authors: Janine F Felix; Leonardo Trasande; Chalana M Sol; Abigail Gaylord; Susana Santos; Vincent W V Jaddoe Journal: Clin Epigenetics Date: 2022-10-10 Impact factor: 7.259