Maternal pre-pregnancy BMI, offspring epigenome-wide DNA methylation, and childhood obesity: findings from the Boston Birth Cohort.

Autor: Si J; Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Meir AY; Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Hong X; Center On the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Wang G; Center On the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Huang W; Department of Civil and Systems Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA., Pearson C; Department of Pediatrics, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA, USA., Adams WG; Department of Pediatrics, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA, USA., Wang X; Center On the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. xwang82@jhu.edu.; Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA. xwang82@jhu.edu., Liang L; Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. lliang@hsph.harvard.edu.
Jazyk: angličtina
Zdroj: BMC medicine [BMC Med] 2023 Aug 23; Vol. 21 (1), pp. 317. Date of Electronic Publication: 2023 Aug 23.
DOI: 10.1186/s12916-023-03003-5
Abstrakt: Background: Maternal pre-pregnancy obesity is an established risk factor for childhood obesity. Investigating epigenetic alterations induced by maternal obesity during fetal development could gain mechanistic insight into the developmental origins of childhood obesity. While obesity disproportionately affects underrepresented racial and ethnic mothers and children in the USA, few studies investigated the role of prenatal epigenetic programming in intergenerational obesity of these high-risk populations.
Methods: This study included 903 mother-child pairs from the Boston Birth Cohort, a predominantly urban, low-income minority birth cohort. Mother-infant dyads were enrolled at birth and the children were followed prospectively to age 18 years. Infinium Methylation EPIC BeadChip was used to measure epigenome-wide methylation level of cord blood. We performed an epigenome-wide association study of maternal pre-pregnancy body mass index (BMI) and cord blood DNA methylation (DNAm). To quantify the degree to which cord blood DNAm mediates the maternal BMI-childhood obesity, we further investigated whether maternal BMI-associated DNAm sites impact birthweight or childhood overweight or obesity (OWO) from age 1 to age 18 and performed corresponding mediation analyses.
Results: The study sample contained 52.8% maternal pre-pregnancy OWO and 63.2% offspring OWO at age 1-18 years. Maternal BMI was associated with cord blood DNAm at 8 CpG sites (genome-wide false discovery rate [FDR] < 0.05). After accounting for the possible interplay of maternal BMI and smoking, 481 CpG sites were discovered for association with maternal BMI. Among them 123 CpGs were associated with childhood OWO, ranging from 42% decrease to 87% increase in OWO risk for each SD increase in DNAm. A total of 14 identified CpG sites showed a significant mediation effect on the maternal BMI-child OWO association (FDR < 0.05), with mediating proportion ranging from 3.99% to 25.21%. Several of these 14 CpGs were mapped to genes in association with energy balance and metabolism (AKAP7) and adulthood metabolic syndrome (CAMK2B).
Conclusions: This prospective birth cohort study in a high-risk yet understudied US population found that maternal pre-pregnancy OWO significantly altered DNAm in newborn cord blood and provided suggestive evidence of epigenetic involvement in the intergenerational risk of obesity.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje