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
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引用次数: 0
Abstract
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.
期刊介绍：
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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