The role of DNA methylation in type 2 diabetes aetiology – using genotype as a causal anchor
The role of DNA methylation in type 2 diabetes aetiology – using genotype as a causal anchor
Several studies have investigated the relationship between genetic variation and DNA methylation with respect to type 2 diabetes but it is unknown if DNA methylation is a mediator in the disease pathway or if it is altered in response to disease state. This study uses genotypic information as a causal anchor to help decipher the likely role of DNA methylation measured in peripheral blood in the aetiology of type 2 diabetes.
Illumina HumanMethylation450 BeadChip data was generated on 1,018 young individuals from the ALSPAC cohort. In stage 1, 118 unique associations between published type 2 diabetes Single Nucleotide Polymorphisms (SNPs) and genome wide methylation (methylation quantitative trait loci; mQTLs) were identified. In stage 2, a further 226 mQTLs were identified between 202 additional independent non-type 2 diabetes SNPs and CpGs identified in stage 1. Where possible, associations were replicated in independent cohorts of similar age.
We discovered that around half of known type 2 diabetes SNPs are associated with variation in DNA methylation and postulated that methylation could either be on a causal pathway to future disease or could be a non-causal biomarker. For one locus (KCNQ1), we were able to provide further evidence that methylation is likely to be on the causal pathway to disease in later life.
1713-1722
Elliot, Hannah
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Shihab, Hashem
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Lockett, Gabrielle A.
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Holloway, John
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McRae, Allan F.
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Davey-Smith, George
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Ring, Susan M.
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Gaunt, Tom R.
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Relton, Caroline L.
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June 2017
Elliot, Hannah
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Shihab, Hashem
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Lockett, Gabrielle A.
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Holloway, John
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McRae, Allan F.
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Davey-Smith, George
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Ring, Susan M.
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Gaunt, Tom R.
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Relton, Caroline L.
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Elliot, Hannah, Shihab, Hashem, Lockett, Gabrielle A., Holloway, John, McRae, Allan F., Davey-Smith, George, Ring, Susan M., Gaunt, Tom R. and Relton, Caroline L.
(2017)
The role of DNA methylation in type 2 diabetes aetiology – using genotype as a causal anchor.
Diabetes, 66 (6), .
(doi:10.2337/db16-0874).
Abstract
Several studies have investigated the relationship between genetic variation and DNA methylation with respect to type 2 diabetes but it is unknown if DNA methylation is a mediator in the disease pathway or if it is altered in response to disease state. This study uses genotypic information as a causal anchor to help decipher the likely role of DNA methylation measured in peripheral blood in the aetiology of type 2 diabetes.
Illumina HumanMethylation450 BeadChip data was generated on 1,018 young individuals from the ALSPAC cohort. In stage 1, 118 unique associations between published type 2 diabetes Single Nucleotide Polymorphisms (SNPs) and genome wide methylation (methylation quantitative trait loci; mQTLs) were identified. In stage 2, a further 226 mQTLs were identified between 202 additional independent non-type 2 diabetes SNPs and CpGs identified in stage 1. Where possible, associations were replicated in independent cohorts of similar age.
We discovered that around half of known type 2 diabetes SNPs are associated with variation in DNA methylation and postulated that methylation could either be on a causal pathway to future disease or could be a non-causal biomarker. For one locus (KCNQ1), we were able to provide further evidence that methylation is likely to be on the causal pathway to disease in later life.
Text
DB16-0874_R1_The role of DNA methylation in type 2 diabetes aetiology_clean
- Accepted Manuscript
More information
Accepted/In Press date: 21 February 2017
e-pub ahead of print date: 28 February 2017
Published date: June 2017
Additional Information:
This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at [insert journal URL: http://diabetes.diabetesjournals.org,
Organisations:
Faculty of Medicine, Human Development & Health, Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 406411
URI: http://eprints.soton.ac.uk/id/eprint/406411
ISSN: 0012-1797
PURE UUID: d3250ffe-56fd-4443-9c3c-79b929141411
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Date deposited: 10 Mar 2017 10:46
Last modified: 16 Mar 2024 02:57
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Contributors
Author:
Hannah Elliot
Author:
Hashem Shihab
Author:
Gabrielle A. Lockett
Author:
Allan F. McRae
Author:
George Davey-Smith
Author:
Susan M. Ring
Author:
Tom R. Gaunt
Author:
Caroline L. Relton
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