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Updated: May 11, 2026

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass
Frédéric Guénard1, Yves Deshaies, Katherine Cianflone
1Institute of Nutrition and Functional Foods and Department of Food Science and Nutrition, Laval University, Quebec City, QC G1V 0A6, Canada.
Insights
Maternal weight loss surgery significantly impacts offspring cardiometabolic health. Children born after surgery show improved metabolic profiles due to lasting changes in their gene methylation and expression.
Area of Science:
- Epigenetics
- Metabolic Health
- Pregnancy Research
Background:
- Maternal obesity and overnutrition during pregnancy can program adult disease risk in offspring.
- Children born after maternal bariatric surgery (AMS) have lower obesity rates and better cardiometabolic profiles than siblings born before surgery (BMS).
Purpose of the Study:
- To investigate the impact of maternal weight loss surgery on gene methylation in offspring.
- To identify biological pathways associated with improved cardiometabolic health in children born after maternal bariatric surgery.
Main Methods:
- Differential methylation analysis was performed on a sibling cohort of 25 BMS and 25 AMS offspring (ages 2-25) from 20 mothers.
- Gene methylation and expression levels were correlated with plasma markers of insulin resistance (fasting insulin, homeostasis model of insulin resistance).
Main Results:
- 5,698 genes showed differential methylation between BMS and AMS siblings, particularly those involved in glucose regulation, inflammation, and vascular disease.
- Correlations between gene methylation, expression, and insulin resistance markers supported metabolic improvements in AMS offspring.
- Findings indicate durable epigenetic and transcriptomic changes in offspring following maternal weight loss surgery.
Conclusions:
- Maternal weight loss surgery leads to lasting, detectable changes in the offspring's methylome and transcriptome.
- These epigenetic modifications are linked to improved cardiometabolic health and reduced insulin resistance in children born after maternal bariatric surgery.
Abstract:
Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2-25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.

