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

Abstract

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.

Association Between DNA Methylation and Blood Pressure: A 5-Year Longitudinal Twin Study

“…These studies were performed on different ethnicities: Africans, East Asians, Europeans, Indian Asians, etc. 7–9,29–33 No obvious tissue-specific epigenomic pattern was revealed in these candidate CpG sites, which was confirmed by applying the eFORGE tool 34 (https://eforge.altiusinstitute.org/; Figure S3).…”

“…Many studies have investigated the associations between DNA methylation and BP and identified hundreds of associated 5′-cytosine-phosphate-guanine-3′ (CpG) sites. [6][7][8][9] However, different studies reported disparate results due to limitations in statistical power, sample sizes, and varying adjustments for important confounders, such as genetic background, which can lead to variability between studies. Twin studies have proven to be a valuable research tool in studying disease-related epigenetic changes, as the twin population is naturally matched for genetic and early-life environmental factors.…”

DNA Methylation Is a Potential Biomarker for Cardiometabolic Health in Mexican Children and Adolescents

“…Previous research highlighted the importance of epigenetics as a potential biomarker for screening, diagnosis, prognosis, and individualized treatment regimens [ 23 , 24 , 29 , 30 , 31 ]. DNA methylation (DNAm), a commonly studied epigenetic modification, has been associated with CVD [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 32 , 33 ] and cardiometabolic risk factors, mainly in adults [ 21 , 28 , 34 , 35 , 36 ]. Existing evidence showed that DNAm during early development was associated with obesity and CVD risk later in life [ 37 ]; early embryogenesis is a particularly sensitive time period for epigenetic alteration by environmental factors that may contribute to disease risk [ 38 ].…”

Supplementation of Methyl-Donor Nutrients to a High-Fat, High-Sucrose Diet during Pregnancy and Lactation Normalizes Circulating 25-Dihydroxycholecalciferol Levels and Alleviates Inflammation in Offspring

“…A recent European prospective cohort study reported a diet rich in methyl-donor nutrients, such as folate, vitamin B 12 , choline, methionine, and betaine, was associated with global methylation changes [26], which were linked to risks of cardiometabolic diseases among offspring [27]. Previously, an in vivo rat study showed that maternal methyldonor nutrient deficiency downregulated the gene expression of VDR and reduced the bioavailability of active VD [28].…”