DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study.
Antoun, Elie;
Issarapu, Prachand;
di Gravio, Chiara;
Shrestha, Smeeta;
Betts, Modupeh;
Saffari, Ayden;
Sahariah, Sirazul A;
Sankareswaran, Alagu;
Arumalla, Manisha;
Prentice, Andrew M;
+5 more...Fall, Caroline HD;
Silver, Matt J;
Chandak, Giriraj R;
Lillycrop, Karen A;
EMPHASIS study group;
EMPHASIS study group;
(2022)
DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study.
Clinical epigenetics, 14 (1).
6-.
ISSN 1868-7075
DOI: https://doi.org/10.1186/s13148-021-01213-3
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BACKGROUND: The prevalence of cardiometabolic disease (CMD) is rising globally, with environmentally induced epigenetic changes suggested to play a role. Few studies have investigated epigenetic associations with CMD risk factors in children from low- and middle-income countries. We sought to identify associations between DNA methylation (DNAm) and CMD risk factors in children from India and The Gambia. RESULTS: Using the Illumina Infinium HumanMethylation 850 K Beadchip array, we interrogated DNAm in 293 Gambian (7-9 years) and 698 Indian (5-7 years) children. We identified differentially methylated CpGs (dmCpGs) associated with systolic blood pressure, fasting insulin, triglycerides and LDL-Cholesterol in the Gambian children; and with insulin sensitivity, insulinogenic index and HDL-Cholesterol in the Indian children. There was no overlap of the dmCpGs between the cohorts. Meta-analysis identified dmCpGs associated with insulin secretion and pulse pressure that were different from cohort-specific dmCpGs. Several differentially methylated regions were associated with diastolic blood pressure, insulin sensitivity and fasting glucose, but these did not overlap with the dmCpGs. We identified significant cis-methQTLs at three LDL-Cholesterol-associated dmCpGs in Gambians; however, methylation did not mediate genotype effects on the CMD outcomes. CONCLUSION: This study identified cardiometabolic biomarkers associated with differential DNAm in Indian and Gambian children. Most associations were cohort specific, potentially reflecting environmental and ethnic differences.