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Background <p>Differences in body composition during childhood can influence long-term health, with notable links to cardiometabolic disorders in later life. While genetic associations with body composition traits are well-studied, less is known about the role of epigenetic mechanisms, particularly in low- and middle-income countries where the burden of cardiometabolic disease is high. We investigated links between DNA methylation and three compartments of body composition: fat mass, lean mass, and bone measures using data from children enrolled in the <i>Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa</i> (EMPHASIS) study.</p> Results <p>We conducted an epigenome-wide association study of 11 body composition traits assessed through dual-energy X-ray absorptiometry in children from India (mean [range] age = 5.8 [5–7] years; n = 686) and The Gambia (age = 9.0 [7–9] years; n = 284), with blood DNA methylation measured at ~ 800,000 CpGs sites on the Illumina EPIC array. Cohort-specific analysis identified 8 unique differentially methylated CpGs associated with traits across all three body composition compartments (<i>p</i> &lt; 3.6 × 10<sup>–8</sup>), with none overlapping both cohorts. Cross-cohort meta-analysis revealed four CpGs associated with lean mass and bone area mapping to <i>SOCS3</i> and <i>ZBTB16</i>. Region-level analyses identified 29 differentially methylated regions (DMRs) in India and 18 in The Gambia. 29 DMRs were identified in the meta-analysis, 25 of which were not detected in either cohort individually. Many DMRs were associated with more than one body composition trait.</p> Conclusion <p>We report novel DNA methylation signatures associated with body composition traits in children from two low- and middle-income countries. Identified loci map to genes linked to inflammatory signalling, energy metabolism and cellular stress response pathways, highlighting a potential role for epigenetic mechanisms in shaping early-life body composition.</p>

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DNA methylation marks associated with body composition in children from India and the Gambia: findings from the EMPHASIS study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Prachand Issarapu,
  • Manisha Arumalla,
  • Elie Antoun,
  • Chiara di Gravio,
  • Kate A. Ward,
  • Caroline H. D. Fall,
  • Andrew M. Prentice,
  • Giriraj Ratan Chandak,
  • Matt J. Silver,
  • Prachand Issarapu,
  • Manisha Arumalla,
  • Smeeta Shrestha,
  • Sara Sajjadi,
  • Sirazul Ameen Sahariah,
  • Ramesh D. Potdar,
  • Harsha Chopra,
  • Harshad Sane,
  • Meera Gandhi,
  • Landing M. A. Jarjou,
  • Ann Prentice,
  • Sarah H. Kehoe,
  • Stephen Owens,
  • Andrew M. Prentice,
  • Matt J. Silver,
  • Giriraj R. Chandak,
  • Caroline H. D. Fall

摘要

Background

Differences in body composition during childhood can influence long-term health, with notable links to cardiometabolic disorders in later life. While genetic associations with body composition traits are well-studied, less is known about the role of epigenetic mechanisms, particularly in low- and middle-income countries where the burden of cardiometabolic disease is high. We investigated links between DNA methylation and three compartments of body composition: fat mass, lean mass, and bone measures using data from children enrolled in the Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa (EMPHASIS) study.

Results

We conducted an epigenome-wide association study of 11 body composition traits assessed through dual-energy X-ray absorptiometry in children from India (mean [range] age = 5.8 [5–7] years; n = 686) and The Gambia (age = 9.0 [7–9] years; n = 284), with blood DNA methylation measured at ~ 800,000 CpGs sites on the Illumina EPIC array. Cohort-specific analysis identified 8 unique differentially methylated CpGs associated with traits across all three body composition compartments (p < 3.6 × 10–8), with none overlapping both cohorts. Cross-cohort meta-analysis revealed four CpGs associated with lean mass and bone area mapping to SOCS3 and ZBTB16. Region-level analyses identified 29 differentially methylated regions (DMRs) in India and 18 in The Gambia. 29 DMRs were identified in the meta-analysis, 25 of which were not detected in either cohort individually. Many DMRs were associated with more than one body composition trait.

Conclusion

We report novel DNA methylation signatures associated with body composition traits in children from two low- and middle-income countries. Identified loci map to genes linked to inflammatory signalling, energy metabolism and cellular stress response pathways, highlighting a potential role for epigenetic mechanisms in shaping early-life body composition.