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Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study

Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in th...

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Autores principales: Kriebel, Jennifer, Herder, Christian, Rathmann, Wolfgang, Wahl, Simone, Kunze, Sonja, Molnos, Sophie, Volkova, Nadezda, Schramm, Katharina, Carstensen-Kirberg, Maren, Waldenberger, Melanie, Gieger, Christian, Peters, Annette, Illig, Thomas, Prokisch, Holger, Roden, Michael, Grallert, Harald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809492/
https://www.ncbi.nlm.nih.gov/pubmed/27019061
http://dx.doi.org/10.1371/journal.pone.0152314
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author Kriebel, Jennifer
Herder, Christian
Rathmann, Wolfgang
Wahl, Simone
Kunze, Sonja
Molnos, Sophie
Volkova, Nadezda
Schramm, Katharina
Carstensen-Kirberg, Maren
Waldenberger, Melanie
Gieger, Christian
Peters, Annette
Illig, Thomas
Prokisch, Holger
Roden, Michael
Grallert, Harald
author_facet Kriebel, Jennifer
Herder, Christian
Rathmann, Wolfgang
Wahl, Simone
Kunze, Sonja
Molnos, Sophie
Volkova, Nadezda
Schramm, Katharina
Carstensen-Kirberg, Maren
Waldenberger, Melanie
Gieger, Christian
Peters, Annette
Illig, Thomas
Prokisch, Holger
Roden, Michael
Grallert, Harald
author_sort Kriebel, Jennifer
collection PubMed
description Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10(-5) and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10(-5) and 3.0x10(-3)). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10(-9)). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes-related traits are associated and that these associations are partially BMI-dependent. Furthermore, the interaction of ABCG1 with glucose metabolism is modulated by epigenetic processes.
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spelling pubmed-48094922016-04-05 Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study Kriebel, Jennifer Herder, Christian Rathmann, Wolfgang Wahl, Simone Kunze, Sonja Molnos, Sophie Volkova, Nadezda Schramm, Katharina Carstensen-Kirberg, Maren Waldenberger, Melanie Gieger, Christian Peters, Annette Illig, Thomas Prokisch, Holger Roden, Michael Grallert, Harald PLoS One Research Article Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10(-5) and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10(-5) and 3.0x10(-3)). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10(-9)). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes-related traits are associated and that these associations are partially BMI-dependent. Furthermore, the interaction of ABCG1 with glucose metabolism is modulated by epigenetic processes. Public Library of Science 2016-03-28 /pmc/articles/PMC4809492/ /pubmed/27019061 http://dx.doi.org/10.1371/journal.pone.0152314 Text en © 2016 Kriebel 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kriebel, Jennifer
Herder, Christian
Rathmann, Wolfgang
Wahl, Simone
Kunze, Sonja
Molnos, Sophie
Volkova, Nadezda
Schramm, Katharina
Carstensen-Kirberg, Maren
Waldenberger, Melanie
Gieger, Christian
Peters, Annette
Illig, Thomas
Prokisch, Holger
Roden, Michael
Grallert, Harald
Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study
title Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study
title_full Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study
title_fullStr Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study
title_full_unstemmed Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study
title_short Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study
title_sort association between dna methylation in whole blood and measures of glucose metabolism: kora f4 study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809492/
https://www.ncbi.nlm.nih.gov/pubmed/27019061
http://dx.doi.org/10.1371/journal.pone.0152314
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