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Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Methylation profiles at birth linked to early childhood obesity
Delphine Lariviere1, Sarah J C Craig2,3, Ian M Paul3,4
1Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA, USA.
Insights
New research reveals that DNA methylation profiles in infants at birth can predict weight gain and obesity risk by six months. These findings highlight epigenomic factors as crucial early indicators for childhood obesity interventions.
Area of Science:
- Epigenetics
- Pediatrics
- Metabolic Health
Background:
- Childhood obesity is a major global health issue requiring identification of early risk factors.
- Genomic, microbiomic, and epigenomic factors are implicated in obesity development.
- Early life epigenetics, specifically DNA methylation, may offer predictive insights into infant weight trajectories.
Purpose of the Study:
- To investigate the association between DNA methylation profiles at birth (cord blood and placenta) and infant weight outcomes at six months.
- To identify specific genes and develop predictive scores related to infant weight gain and obesity risk.
- To explore the role of epigenomic modifications in early-life obesity development.
Main Methods:
- Genome-wide DNA methylation profiling using the Illumina Infinium MethylationEpic chip in 48 infants.
- Analysis incorporating child/maternal health and environmental factors.
- Regression analysis to identify methylation profiles predictive of weight outcomes (conditional weight gain, BMI, weight-for-length ratio).
Main Results:
- Identified 23 predictive genes in cord blood and 10 in placenta associated with infant weight outcomes.
- Three cord blood genes (PLIN4, UBE2F, PPP1R16B) consistently predicted all three weight outcomes and were validated in an independent cohort.
- Developed a Methylation Risk Score (MRS) to identify infants at higher risk for childhood obesity.
Conclusions:
- Infant DNA methylation profiles at birth are significantly associated with weight outcomes in the first six months of life.
- Specific genes and the developed MRS show potential for early identification of children at risk of obesity.
- These findings underscore the importance of epigenomic factors in early-life obesity and warrant further functional investigation.
Abstract:
Childhood obesity represents a significant global health concern and identifying its risk factors is crucial for developing intervention programs. Many "omics" factors associated with the risk of developing obesity have been identified, including genomic, microbiomic, and epigenomic factors. Here, using a sample of 48 infants, we investigated how the methylation profiles in cord blood and placenta at birth were associated with weight outcomes (specifically, conditional weight gain, body mass index, and weight-for-length ratio) at age six months. We characterized genome-wide DNA methylation profiles using the Illumina Infinium MethylationEpic chip, and incorporated information on child and maternal health, and various environmental factors into the analysis. We used regression analysis to identify genes with methylation profiles most predictive of infant weight outcomes, finding a total of 23 relevant genes in cord blood and 10 in placenta. Notably, in cord blood, the methylation profiles of three genes (PLIN4, UBE2F, and PPP1R16B) were associated with all three weight outcomes, which are also associated with weight outcomes in an independent cohort suggesting a strong relationship with weight trajectories in the first six months after birth. Additionally, we developed a Methylation Risk Score (MRS) that could be used to identify children most at risk for developing childhood obesity. While many of the genes identified by our analysis have been associated with weight-related traits (e.g., glucose metabolism, BMI, or hip-to-waist ratio) in previous genome-wide association and variant studies, our analysis implicated several others, whose involvement in the obesity phenotype should be evaluated in future functional investigations.
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