Offspring epigenetic markers at birth related to gestational BMI predict offspring BMI-trajectories from infancy to 26 years.

Objective: To date, epigenetic studies identified differential DNA methylation (DNAm) related to gestational-body mass index (BMI) in offspring at birth. This study investigated whether the identified DNAm in offspring were also associated with BMI trajectories from infancy to age 26 years.

Methods: Data of 794 participants from Isle of Wight birth cohort in UK were investigated to study association between BMI trajectories and DNAm related to gestational-BMI at birth. Multinominal logistic regression models were applied to test the association between 1090 DNAm sites reported in three prior epigenome-wide association studies and BMI trajectories.

Results: DNAm site cg23089913 (NANOS1) and cg13217064 (SOX14) were associated with early persistent obesity (EPO) and delayed overweight (DOW) trajectories respectively. A higher methylation of cg23089913 showed low odds of being in EPO trajectory (OR: 0.84; 95% CI: 0.76-0.93) while higher methylation of cg13217064 resulted in 1.4-times the odds of being in DOW trajectory when compared to the normal trajectory [Correction added on 22 February 2023, after first online publication: Range of the DNAm site cg23089913 has been changed from 'lower' to 'higher' in the preceding sentence.]. In a gender-stratified analysis, the odds of developing into DOW was 1.8 times in female participants for cg13217064 while not such association was observed in males.

Conclusions: Deviations in methylation of cg23089913 (NANOS1) and cg13217064 (SOX14) in newborns may change the risk of having excess body weight.