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An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis
Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of...
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2019
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565679/ https://www.ncbi.nlm.nih.gov/pubmed/31197173 http://dx.doi.org/10.1038/s41467-019-10487-4 |
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| author | Liu, Jun Carnero-Montoro, Elena van Dongen, Jenny Lent, Samantha Nedeljkovic, Ivana Ligthart, Symen Tsai, Pei-Chien Martin, Tiphaine C. Mandaviya, Pooja R. Jansen, Rick Peters, Marjolein J. Duijts, Liesbeth Jaddoe, Vincent W. V. Tiemeier, Henning Felix, Janine F. Willemsen, Gonneke de Geus, Eco J. C. Chu, Audrey Y. Levy, Daniel Hwang, Shih-Jen Bressler, Jan Gondalia, Rahul Salfati, Elias L. Herder, Christian Hidalgo, Bertha A. Tanaka, Toshiko Moore, Ann Zenobia Lemaitre, Rozenn N. Jhun, Min A Smith, Jennifer A. Sotoodehnia, Nona Bandinelli, Stefania Ferrucci, Luigi Arnett, Donna K. Grallert, Harald Assimes, Themistocles L. Hou, Lifang Baccarelli, Andrea Whitsel, Eric A. van Dijk, Ko Willems Amin, Najaf Uitterlinden, André G. Sijbrands, Eric J. G. Franco, Oscar H. Dehghan, Abbas Spector, Tim D. Dupuis, Josée Hivert, Marie-France Rotter, Jerome I. Meigs, James B. Pankow, James S. van Meurs, Joyce B. J. Isaacs, Aaron Boomsma, Dorret I. Bell, Jordana T. Demirkan, Ayşe van Duijn, Cornelia M. |
| author_facet | Liu, Jun Carnero-Montoro, Elena van Dongen, Jenny Lent, Samantha Nedeljkovic, Ivana Ligthart, Symen Tsai, Pei-Chien Martin, Tiphaine C. Mandaviya, Pooja R. Jansen, Rick Peters, Marjolein J. Duijts, Liesbeth Jaddoe, Vincent W. V. Tiemeier, Henning Felix, Janine F. Willemsen, Gonneke de Geus, Eco J. C. Chu, Audrey Y. Levy, Daniel Hwang, Shih-Jen Bressler, Jan Gondalia, Rahul Salfati, Elias L. Herder, Christian Hidalgo, Bertha A. Tanaka, Toshiko Moore, Ann Zenobia Lemaitre, Rozenn N. Jhun, Min A Smith, Jennifer A. Sotoodehnia, Nona Bandinelli, Stefania Ferrucci, Luigi Arnett, Donna K. Grallert, Harald Assimes, Themistocles L. Hou, Lifang Baccarelli, Andrea Whitsel, Eric A. van Dijk, Ko Willems Amin, Najaf Uitterlinden, André G. Sijbrands, Eric J. G. Franco, Oscar H. Dehghan, Abbas Spector, Tim D. Dupuis, Josée Hivert, Marie-France Rotter, Jerome I. Meigs, James B. Pankow, James S. van Meurs, Joyce B. J. Isaacs, Aaron Boomsma, Dorret I. Bell, Jordana T. Demirkan, Ayşe van Duijn, Cornelia M. |
| author_sort | Liu, Jun |
| collection | PubMed |
| description | Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D. |
| format | Online Article Text |
| id | pubmed-6565679 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-65656792019-06-21 An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis Liu, Jun Carnero-Montoro, Elena van Dongen, Jenny Lent, Samantha Nedeljkovic, Ivana Ligthart, Symen Tsai, Pei-Chien Martin, Tiphaine C. Mandaviya, Pooja R. Jansen, Rick Peters, Marjolein J. Duijts, Liesbeth Jaddoe, Vincent W. V. Tiemeier, Henning Felix, Janine F. Willemsen, Gonneke de Geus, Eco J. C. Chu, Audrey Y. Levy, Daniel Hwang, Shih-Jen Bressler, Jan Gondalia, Rahul Salfati, Elias L. Herder, Christian Hidalgo, Bertha A. Tanaka, Toshiko Moore, Ann Zenobia Lemaitre, Rozenn N. Jhun, Min A Smith, Jennifer A. Sotoodehnia, Nona Bandinelli, Stefania Ferrucci, Luigi Arnett, Donna K. Grallert, Harald Assimes, Themistocles L. Hou, Lifang Baccarelli, Andrea Whitsel, Eric A. van Dijk, Ko Willems Amin, Najaf Uitterlinden, André G. Sijbrands, Eric J. G. Franco, Oscar H. Dehghan, Abbas Spector, Tim D. Dupuis, Josée Hivert, Marie-France Rotter, Jerome I. Meigs, James B. Pankow, James S. van Meurs, Joyce B. J. Isaacs, Aaron Boomsma, Dorret I. Bell, Jordana T. Demirkan, Ayşe van Duijn, Cornelia M. Nat Commun Article Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D. Nature Publishing Group UK 2019-06-13 /pmc/articles/PMC6565679/ /pubmed/31197173 http://dx.doi.org/10.1038/s41467-019-10487-4 Text en © Crown 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Liu, Jun Carnero-Montoro, Elena van Dongen, Jenny Lent, Samantha Nedeljkovic, Ivana Ligthart, Symen Tsai, Pei-Chien Martin, Tiphaine C. Mandaviya, Pooja R. Jansen, Rick Peters, Marjolein J. Duijts, Liesbeth Jaddoe, Vincent W. V. Tiemeier, Henning Felix, Janine F. Willemsen, Gonneke de Geus, Eco J. C. Chu, Audrey Y. Levy, Daniel Hwang, Shih-Jen Bressler, Jan Gondalia, Rahul Salfati, Elias L. Herder, Christian Hidalgo, Bertha A. Tanaka, Toshiko Moore, Ann Zenobia Lemaitre, Rozenn N. Jhun, Min A Smith, Jennifer A. Sotoodehnia, Nona Bandinelli, Stefania Ferrucci, Luigi Arnett, Donna K. Grallert, Harald Assimes, Themistocles L. Hou, Lifang Baccarelli, Andrea Whitsel, Eric A. van Dijk, Ko Willems Amin, Najaf Uitterlinden, André G. Sijbrands, Eric J. G. Franco, Oscar H. Dehghan, Abbas Spector, Tim D. Dupuis, Josée Hivert, Marie-France Rotter, Jerome I. Meigs, James B. Pankow, James S. van Meurs, Joyce B. J. Isaacs, Aaron Boomsma, Dorret I. Bell, Jordana T. Demirkan, Ayşe van Duijn, Cornelia M. An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis |
| title | An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis |
| title_full | An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis |
| title_fullStr | An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis |
| title_full_unstemmed | An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis |
| title_short | An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis |
| title_sort | integrative cross-omics analysis of dna methylation sites of glucose and insulin homeostasis |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565679/ https://www.ncbi.nlm.nih.gov/pubmed/31197173 http://dx.doi.org/10.1038/s41467-019-10487-4 |
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