Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: a cross-sectional study

Prasoon Agarwal; Brandy A. Wicklow; Allison B. Dart; Nikho A. Hizon; Elizabeth A.c. Sellers; Jonathan M. Mcgavock; Charlotte P. J. Talbot; Mario A. Fonseca; Wayne Xu; James R. Davie; Meaghan J. Jones; Animesh Acharjee; Vernon W. Dolinsky

doi:10.3389/fendo.2022.934706

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: a cross-sectional study

Prasoon Agarwal, Brandy A. Wicklow, Allison B. Dart, Nikho A. Hizon, Elizabeth A.c. Sellers, Jonathan M. Mcgavock, Charlotte P. J. Talbot, Mario A. Fonseca, Wayne Xu, James R. Davie, Meaghan J. Jones, Animesh Acharjee, Vernon W. Dolinsky

Cancer and Genomic Sciences

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Abstract

Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D.

Methods: We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D.

Results: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others.

Conclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.

Original language	English
Article number	934706
Number of pages	16
Journal	Frontiers in Endocrinology
Volume	13
DOIs	https://doi.org/10.3389/fendo.2022.934706
Publication status	Published - 10 Oct 2022

Keywords

Diabetes
Integrative analyses
Machine Learning
Metabolomics
methylation
multiomics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Agarwal, P., Wicklow, B. A., Dart, A. B., Hizon, N. A., Sellers, E. A. C., Mcgavock, J. M., Talbot, C. P. J., Fonseca, M. A., Xu, W., Davie, J. R., Jones, M. J., Acharjee, A., & Dolinsky, V. W. (2022). Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: a cross-sectional study. Frontiers in Endocrinology, 13, Article 934706. https://doi.org/10.3389/fendo.2022.934706

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title = "Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: a cross-sectional study",

abstract = "Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D.Methods: We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D.Results: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others.Conclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.",

keywords = "Diabetes, Integrative analyses, Machine Learning, Metabolomics, methylation, multiomics",

author = "Prasoon Agarwal and Wicklow, {Brandy A.} and Dart, {Allison B.} and Hizon, {Nikho A.} and Sellers, {Elizabeth A.c.} and Mcgavock, {Jonathan M.} and Talbot, {Charlotte P. J.} and Fonseca, {Mario A.} and Wayne Xu and Davie, {James R.} and Jones, {Meaghan J.} and Animesh Acharjee and Dolinsky, {Vernon W.}",

year = "2022",

month = oct,

day = "10",

doi = "10.3389/fendo.2022.934706",

language = "English",

volume = "13",

journal = "Frontiers in Endocrinology",

issn = "1664-2392",

publisher = "Frontiers",

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Agarwal, P, Wicklow, BA, Dart, AB, Hizon, NA, Sellers, EAC, Mcgavock, JM, Talbot, CPJ, Fonseca, MA, Xu, W, Davie, JR, Jones, MJ, Acharjee, A & Dolinsky, VW 2022, 'Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: a cross-sectional study', Frontiers in Endocrinology, vol. 13, 934706. https://doi.org/10.3389/fendo.2022.934706

TY - JOUR

T1 - Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes

T2 - a cross-sectional study

AU - Agarwal, Prasoon

AU - Wicklow, Brandy A.

AU - Dart, Allison B.

AU - Hizon, Nikho A.

AU - Sellers, Elizabeth A.c.

AU - Mcgavock, Jonathan M.

AU - Talbot, Charlotte P. J.

AU - Fonseca, Mario A.

AU - Xu, Wayne

AU - Davie, James R.

AU - Jones, Meaghan J.

AU - Acharjee, Animesh

AU - Dolinsky, Vernon W.

PY - 2022/10/10

Y1 - 2022/10/10

N2 - Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D.Methods: We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D.Results: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others.Conclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.

AB - Objective: Rates of type 2 diabetes (T2D) among adolescents are on the rise. Epigenetic changes could be associated with the metabolic alterations in adolescents with T2D.Methods: We performed a cross sectional integrated analysis of DNA methylation data from peripheral blood mononuclear cells with serum metabolomic data from First Nation adolescents with T2D and controls participating in the Improving Renal Complications in Adolescents with type 2 diabetes through Research (iCARE) cohort study, to explore the molecular changes in adolescents with T2D.Results: Our analysis showed that 43 serum metabolites and 36 differentially methylated regions (DMR) were associated with T2D. Several DMRs were located near the transcriptional start site of genes with established roles in metabolic disease and associated with altered serum metabolites (e.g. glucose, leucine, and gamma-glutamylisoleucine). These included the free fatty acid receptor-1 (FFAR1), upstream transcription factor-2 (USF2), and tumor necrosis factor-related protein-9 (C1QTNF9), among others.Conclusions: We identified DMRs and metabolites that merit further investigation to determine their significance in controlling gene expression and metabolism which could define T2D risk in adolescents.

KW - Diabetes

KW - Integrative analyses

KW - Machine Learning

KW - Metabolomics

KW - methylation

KW - multiomics

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U2 - 10.3389/fendo.2022.934706

DO - 10.3389/fendo.2022.934706

M3 - Article

SN - 1664-2392

VL - 13

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 934706

ER -

Integrative analysis reveals novel associations between DNA methylation and the serum metabolome of adolescents with type 2 diabetes: a cross-sectional study

Abstract

Keywords

UN SDGs

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