Body Mass Index Drives Changes in DNA Methylation: A Longitudinal Study

Area of Science:

• Epigenetics
• Human Genetics
• Metabolic Disease Research

Background:

• Epigenome-Wide Association Studies (EWASs) suggest obesity may influence DNA methylation (DNAm) rather than being solely a consequence.
• Longitudinal data are needed to establish the causal relationship between obesity and DNAm changes.

Purpose of the Study:

• To identify specific DNA methylation (CpG) sites associated with body mass index (BMI).
• To investigate the temporal relationship between dynamic DNAm changes and BMI in a longitudinal cohort.

Main Methods:

• Race-specific EWASs were conducted in white and black participants from the Bogalusa Heart Study and Georgia Stress and Heart Study.
• Cross-lagged panel analysis examined the temporal relationship between DNAm and BMI over approximately 6.2 years.
• DNAm scores were calculated from associated CpG sites.

Main Results:

• 349 CpG sites (266 novel) in whites and 36 (21 novel) in blacks were robustly associated with BMI.
• Significant unidirectional paths from baseline BMI to follow-up DNAm were observed in both racial groups.
• No significant paths were found from baseline DNAm to follow-up BMI.

Conclusions:

• Findings provide strong evidence that obesity is a cause of DNAm changes over time.
• The temporal relationship indicates BMI influences epigenetic modifications, not vice versa.