DNA methylation and type 2 diabetes: the use of Mendelian randomization to assess causality

Diana L Juvinao-Quintero; Marie-France Hivert; Gemma C Sharp; Caroline L Relton; Hannah R Elliott

doi:10.1007/s40142-019-00176-5

DNA methylation and type 2 diabetes: the use of Mendelian randomization to assess causality

Diana L Juvinao-Quintero, Marie-France Hivert, Gemma C Sharp, Caroline L Relton, Hannah R Elliott

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Abstract

Purpose of Review
This review summarises recent advances in the field of epigenetics in order to understand the aetiology of type 2 diabetes (T2D).

Recent Findings
DNA methylation at a number of loci has been shown to be robustly associated with T2D, including TXNIP, ABCG1, CPT1A, and SREBF1. However, due to the cross-sectional nature of many epidemiological studies and predominant analysis in samples derived from blood rather than disease relevant tissues, inferring causality is difficult. We therefore outline the use of Mendelian randomisation (MR) as one method able to assess causality in epigenetic studies of T2D.

Summary
Epidemiological studies have been fruitful in identifying epigenetic markers of T2D. Triangulation of evidence including utilisation of MR is essential to delineate causal from non-causal biomarkers of disease. Understanding the causality of epigenetic markers in T2D more fully will aid prioritisation of CpG sites as early biomarkers to detect disease or in drug development to target epigenetic mechanisms in order to treat patients.

Original language	English
Pages (from-to)	191–207
Number of pages	17
Journal	Current Genetic Medicine Reports
Volume	7
Early online date	15 Nov 2019
DOIs	https://doi.org/10.1007/s40142-019-00176-5
Publication status	Published - 1 Dec 2019

Bibliographical note

The acceptance date for this record is provisional and based upon the month of publication for the article.

Keywords

Type 2 diabetes
DNA methylation
Biomarkers
Causal inference methods
Mendelian randomisation

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3 Finished

IEU 2 Relton Programme - Epigenetic Epidemiology
Relton, C. L.
1/04/18 → 31/03/23
Project: Research
EPoCH: Rework of Prenatal influences on childhood health: what role for mums and dads? (IEU)
Sharp, G. C. & Easey, K. E.
3/06/19 → 30/09/22
Project: Research
NutriPROGRAM: NutriPro for MRC
Sharp, G. C. & Johnson, L.
1/03/19 → 31/08/22
Project: Research

HPC (High Performance Computing) Facility
Sadaf R Alam (Manager), Steven A Chapman (Manager), Polly E Eccleston (Other), Simon H Atack (Other) & D A G Williams (Manager)
Facility/equipment: Facility

Cite this

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title = "DNA methylation and type 2 diabetes: the use of Mendelian randomization to assess causality",

abstract = "Purpose of ReviewThis review summarises recent advances in the field of epigenetics in order to understand the aetiology of type 2 diabetes (T2D).Recent FindingsDNA methylation at a number of loci has been shown to be robustly associated with T2D, including TXNIP, ABCG1, CPT1A, and SREBF1. However, due to the cross-sectional nature of many epidemiological studies and predominant analysis in samples derived from blood rather than disease relevant tissues, inferring causality is difficult. We therefore outline the use of Mendelian randomisation (MR) as one method able to assess causality in epigenetic studies of T2D.SummaryEpidemiological studies have been fruitful in identifying epigenetic markers of T2D. Triangulation of evidence including utilisation of MR is essential to delineate causal from non-causal biomarkers of disease. Understanding the causality of epigenetic markers in T2D more fully will aid prioritisation of CpG sites as early biomarkers to detect disease or in drug development to target epigenetic mechanisms in order to treat patients.",

keywords = "Type 2 diabetes, DNA methylation, Biomarkers, Causal inference methods, Mendelian randomisation",

author = "Juvinao-Quintero, {Diana L} and Marie-France Hivert and Sharp, {Gemma C} and Relton, {Caroline L} and Elliott, {Hannah R}",

note = "The acceptance date for this record is provisional and based upon the month of publication for the article.",

year = "2019",

month = dec,

day = "1",

doi = "10.1007/s40142-019-00176-5",

language = "English",

volume = "7",

pages = "191–207",

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T1 - DNA methylation and type 2 diabetes

T2 - the use of Mendelian randomization to assess causality

AU - Juvinao-Quintero, Diana L

AU - Hivert, Marie-France

AU - Sharp, Gemma C

AU - Relton, Caroline L

AU - Elliott, Hannah R

N1 - The acceptance date for this record is provisional and based upon the month of publication for the article.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Purpose of ReviewThis review summarises recent advances in the field of epigenetics in order to understand the aetiology of type 2 diabetes (T2D).Recent FindingsDNA methylation at a number of loci has been shown to be robustly associated with T2D, including TXNIP, ABCG1, CPT1A, and SREBF1. However, due to the cross-sectional nature of many epidemiological studies and predominant analysis in samples derived from blood rather than disease relevant tissues, inferring causality is difficult. We therefore outline the use of Mendelian randomisation (MR) as one method able to assess causality in epigenetic studies of T2D.SummaryEpidemiological studies have been fruitful in identifying epigenetic markers of T2D. Triangulation of evidence including utilisation of MR is essential to delineate causal from non-causal biomarkers of disease. Understanding the causality of epigenetic markers in T2D more fully will aid prioritisation of CpG sites as early biomarkers to detect disease or in drug development to target epigenetic mechanisms in order to treat patients.

AB - Purpose of ReviewThis review summarises recent advances in the field of epigenetics in order to understand the aetiology of type 2 diabetes (T2D).Recent FindingsDNA methylation at a number of loci has been shown to be robustly associated with T2D, including TXNIP, ABCG1, CPT1A, and SREBF1. However, due to the cross-sectional nature of many epidemiological studies and predominant analysis in samples derived from blood rather than disease relevant tissues, inferring causality is difficult. We therefore outline the use of Mendelian randomisation (MR) as one method able to assess causality in epigenetic studies of T2D.SummaryEpidemiological studies have been fruitful in identifying epigenetic markers of T2D. Triangulation of evidence including utilisation of MR is essential to delineate causal from non-causal biomarkers of disease. Understanding the causality of epigenetic markers in T2D more fully will aid prioritisation of CpG sites as early biomarkers to detect disease or in drug development to target epigenetic mechanisms in order to treat patients.

KW - Type 2 diabetes

KW - DNA methylation

KW - Biomarkers

KW - Causal inference methods

KW - Mendelian randomisation

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DO - 10.1007/s40142-019-00176-5

M3 - Review article (Academic Journal)

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VL - 7

SP - 191

EP - 207

JO - Current Genetic Medicine Reports

JF - Current Genetic Medicine Reports

SN - 2167-4876

ER -

DNA methylation and type 2 diabetes: the use of Mendelian randomization to assess causality

Abstract

Bibliographical note

Keywords

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Projects

IEU 2 Relton Programme - Epigenetic Epidemiology

EPoCH: Rework of Prenatal influences on childhood health: what role for mums and dads? (IEU)

NutriPROGRAM: NutriPro for MRC

Equipment

HPC (High Performance Computing) Facility

Cite this