The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue

The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue

Genetic variants that associate with DNA methylation at CpG sites (methylation quantitative trait loci, meQTLs) offer a potential biological mechanism of action for disease associated SNPs. We investigated whether meQTLs exist in abdominal subcutaneous adipose tissue (SAT) and if CpG methylation ass...

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Main Authors: Drong, Alexander W., Nicholson, George, Hedman, Åsa K., Meduri, Eshwar, Grundberg, Elin, Small, Kerrin S., Shin, So-Youn, Bell, Jordana T., Karpe, Fredrik, Soranzo, Nicole, Spector, Tim D., McCarthy, Mark I., Deloukas, Panos, Rantalainen, Mattias, Lindgren, Cecilia M.
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576415/
id pubmed-3576415
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spelling pubmed-35764152013-02-21 The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue Drong, Alexander W. Nicholson, George Hedman, Åsa K. Meduri, Eshwar Grundberg, Elin Small, Kerrin S. Shin, So-Youn Bell, Jordana T. Karpe, Fredrik Soranzo, Nicole Spector, Tim D. McCarthy, Mark I. Deloukas, Panos Rantalainen, Mattias Lindgren, Cecilia M. Research Article Genetic variants that associate with DNA methylation at CpG sites (methylation quantitative trait loci, meQTLs) offer a potential biological mechanism of action for disease associated SNPs. We investigated whether meQTLs exist in abdominal subcutaneous adipose tissue (SAT) and if CpG methylation associates with metabolic syndrome (MetSyn) phenotypes. We profiled 27,718 genomic regions in abdominal SAT samples of 38 unrelated individuals using differential methylation hybridization (DMH) together with genotypes at 5,227,243 SNPs and expression of 17,209 mRNA transcripts. Validation and replication of significant meQTLs was pursued in an independent cohort of 181 female twins. We find that, at 5% false discovery rate, methylation levels of 149 DMH regions associate with at least one SNP in a ±500 kilobase cis-region in our primary study. We sought to validate 19 of these in the replication study and find that five of these significantly associate with the corresponding meQTL SNPs from the primary study. We find that none of the 149 meQTL top SNPs is a significant expression quantitative trait locus in our expression data, but we observed association between expression levels of two mRNA transcripts and cis-methylation status. Our results indicate that DNA CpG methylation in abdominal SAT is partly under genetic control. This study provides a starting point for future investigations of DNA methylation in adipose tissue. Public Library of Science 2013-02-19 /pmc/articles/PMC3576415/ /pubmed/23431366 http://dx.doi.org/10.1371/journal.pone.0055923 Text en © 2013 Drong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Drong, Alexander W.
Nicholson, George
Hedman, Åsa K.
Meduri, Eshwar
Grundberg, Elin
Small, Kerrin S.
Shin, So-Youn
Bell, Jordana T.
Karpe, Fredrik
Soranzo, Nicole
Spector, Tim D.
McCarthy, Mark I.
Deloukas, Panos
Rantalainen, Mattias
Lindgren, Cecilia M.
spellingShingle Drong, Alexander W.
Nicholson, George
Hedman, Åsa K.
Meduri, Eshwar
Grundberg, Elin
Small, Kerrin S.
Shin, So-Youn
Bell, Jordana T.
Karpe, Fredrik
Soranzo, Nicole
Spector, Tim D.
McCarthy, Mark I.
Deloukas, Panos
Rantalainen, Mattias
Lindgren, Cecilia M.
The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue
author_facet Drong, Alexander W.
Nicholson, George
Hedman, Åsa K.
Meduri, Eshwar
Grundberg, Elin
Small, Kerrin S.
Shin, So-Youn
Bell, Jordana T.
Karpe, Fredrik
Soranzo, Nicole
Spector, Tim D.
McCarthy, Mark I.
Deloukas, Panos
Rantalainen, Mattias
Lindgren, Cecilia M.
author_sort Drong, Alexander W.
title The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue
title_short The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue
title_full The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue
title_fullStr The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue
title_full_unstemmed The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue
title_sort presence of methylation quantitative trait loci indicates a direct genetic influence on the level of dna methylation in adipose tissue
description Genetic variants that associate with DNA methylation at CpG sites (methylation quantitative trait loci, meQTLs) offer a potential biological mechanism of action for disease associated SNPs. We investigated whether meQTLs exist in abdominal subcutaneous adipose tissue (SAT) and if CpG methylation associates with metabolic syndrome (MetSyn) phenotypes. We profiled 27,718 genomic regions in abdominal SAT samples of 38 unrelated individuals using differential methylation hybridization (DMH) together with genotypes at 5,227,243 SNPs and expression of 17,209 mRNA transcripts. Validation and replication of significant meQTLs was pursued in an independent cohort of 181 female twins. We find that, at 5% false discovery rate, methylation levels of 149 DMH regions associate with at least one SNP in a ±500 kilobase cis-region in our primary study. We sought to validate 19 of these in the replication study and find that five of these significantly associate with the corresponding meQTL SNPs from the primary study. We find that none of the 149 meQTL top SNPs is a significant expression quantitative trait locus in our expression data, but we observed association between expression levels of two mRNA transcripts and cis-methylation status. Our results indicate that DNA CpG methylation in abdominal SAT is partly under genetic control. This study provides a starting point for future investigations of DNA methylation in adipose tissue.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576415/
_version_ 1611956136047542272

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