DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study

Journal article

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

Authors: Antoun, E; Issarapu, P; di Gravio, C; Shrestha, S; Betts, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Clinical Epigenetics
• Volume: 14
• Issue: 1
• Pages: 6-6
• Article number: 6
• Publication date: 2022-01-09
• DOI: 10.1186/s13148-021-01213-3
• EISSN: 1868-7083
• ISSN: 1868-7075
• Language: English
• Keywords: Bioinformatics; Endocrinology; Body mass index; Internal medicine; Genetics; Insulin; dNaM; DNA methylation; Biology; Medicine; Epigenetics; Gene; Blood pressure; Cohort study; Cohort; Methylation