DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study
DNA methylation signatures associated with cardiometabolic risk factors in children from India and The Gambia: results from the EMPHASIS study
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.
Biomarkers, Cardiometabolic Risk Factors, Child, Child, Preschool, Cohort Studies, DNA Methylation/genetics, Epigenesis, Genetic, Female, Gambia/epidemiology, Genetic Predisposition to Disease, Humans, India/epidemiology, Male, Metabolic Syndrome/epidemiology, Prevalence
Antoun, Elie
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Issarapu, Prachand
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di Gravio, Chiara
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Shrestha, Smeeta
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Betts, Modupeh
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Saffari, Ayden
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Sahariah, Sirazul A.
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Sankareswaran, Alagu
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Arumalla, Manisha
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Prentice, Andrew M.
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Fall, Caroline H.D.
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Silver, Matt J.
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Chandak, Giriraj R.
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Lillycrop, Karen A.
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9 January 2022
Antoun, Elie
23e4ee54-9652-41cd-9eb0-066cfcc598c9
Issarapu, Prachand
f980880e-53a1-477d-affc-7a2f7328504b
di Gravio, Chiara
4033fc31-5d17-4329-b741-aee8ba31d971
Shrestha, Smeeta
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Betts, Modupeh
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Saffari, Ayden
586ef334-e08f-4ca0-b2f6-575a453d5fa3
Sahariah, Sirazul A.
00647542-3ca0-44e4-b3bc-f0c84228f7e6
Sankareswaran, Alagu
94d78d8d-233c-4be4-b580-52879792255b
Arumalla, Manisha
00fae54e-66e8-4257-877f-59d1c65ce265
Prentice, Andrew M.
6b851f61-f989-48f6-8109-9a7408254728
Fall, Caroline H.D.
7171a105-34f5-4131-89d7-1aa639893b18
Silver, Matt J.
b80ecb7f-b011-4f37-9b9a-d0c63f1979c4
Chandak, Giriraj R.
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Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Antoun, Elie, Issarapu, Prachand, di Gravio, Chiara, Shrestha, Smeeta, Betts, Modupeh, Saffari, Ayden, Sahariah, Sirazul A., Sankareswaran, Alagu, Arumalla, Manisha, Prentice, Andrew M., Fall, Caroline H.D., Silver, Matt J., Chandak, Giriraj R. and Lillycrop, Karen A.
,
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, [6].
(doi:10.1186/s13148-021-01213-3).
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.
Text
s13148-021-01213-3
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More information
Accepted/In Press date: 8 December 2021
Published date: 9 January 2022
Keywords:
Biomarkers, Cardiometabolic Risk Factors, Child, Child, Preschool, Cohort Studies, DNA Methylation/genetics, Epigenesis, Genetic, Female, Gambia/epidemiology, Genetic Predisposition to Disease, Humans, India/epidemiology, Male, Metabolic Syndrome/epidemiology, Prevalence
Identifiers
Local EPrints ID: 485810
URI: http://eprints.soton.ac.uk/id/eprint/485810
ISSN: 1868-7075
PURE UUID: 51cfd69b-5e1d-48a9-ab2d-8f91dfb594ae
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Date deposited: 19 Dec 2023 18:01
Last modified: 18 Mar 2024 02:41
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Contributors
Author:
Elie Antoun
Author:
Prachand Issarapu
Author:
Chiara di Gravio
Author:
Smeeta Shrestha
Author:
Modupeh Betts
Author:
Ayden Saffari
Author:
Sirazul A. Sahariah
Author:
Alagu Sankareswaran
Author:
Manisha Arumalla
Author:
Andrew M. Prentice
Author:
Matt J. Silver
Author:
Giriraj R. Chandak
Corporate Author: EMPHASIS Study Group
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