An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

Jun Liu; Elena Carnero-Montoro; Jenny van Dongen; Samantha Lent; Ivana Nedeljkovic; Symen Ligthart; Pei Chien Tsai; Tiphaine C. Martin; Pooja R. Mandaviya; Rick Jansen; Marjolein J. Peters; Liesbeth Duijts; Vincent W.V. Jaddoe; Henning Tiemeier; Janine F. Felix; Gonneke Willemsen; Eco J.C. de Geus; Audrey Y. Chu; Daniel Levy; Shih Jen Hwang; Jan Bressler; Rahul Gondalia; Elias L. Salfati; Christian Herder; Bertha A. Hidalgo; Toshiko Tanaka; Ann Zenobia Moore; Rozenn N. Lemaitre; Min A. Jhun; Jennifer A. Smith; Nona Sotoodehnia; Stefania Bandinelli; Luigi Ferrucci; Donna K. Arnett; Harald Grallert; Themistocles L. Assimes; Lifang Hou; Andrea Baccarelli; Eric A. Whitsel; Ko Willems van Dijk; Najaf Amin; André G. Uitterlinden; Eric J.G. Sijbrands; Oscar H. Franco; Abbas Dehghan; Tim D. Spector; Josée Dupuis; Marie France Hivert; Jerome I. Rotter; James B. Meigs; James S. Pankow; Joyce B.J. van Meurs; Aaron Isaacs; Dorret I. Boomsma; Jordana T. Bell; Ayşe Demirkan; Cornelia M. van Duijn

doi:10.1038/s41467-019-10487-4

An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

Jun Liu^*
, Elena Carnero-Montoro
, Jenny van Dongen
, Samantha Lent
, Ivana Nedeljkovic
, Symen Ligthart
, Pei Chien Tsai
, Tiphaine C. Martin
, Pooja R. Mandaviya
, Rick Jansen
, Marjolein J. Peters
, Liesbeth Duijts
, Vincent W.V. Jaddoe
, Henning Tiemeier
, Janine F. Felix
, Gonneke Willemsen
, Eco J.C. de Geus
, Audrey Y. Chu
, Daniel Levy
, Shih Jen Hwang

Jan Bressler, Rahul Gondalia, Elias L. Salfati, Christian Herder, Bertha A. Hidalgo, Toshiko Tanaka, Ann Zenobia Moore, Rozenn N. Lemaitre, Min A. Jhun, Jennifer A. Smith, Nona Sotoodehnia, Stefania Bandinelli, Luigi Ferrucci, Donna K. Arnett, Harald Grallert, Themistocles L. Assimes, Lifang Hou, Andrea Baccarelli, Eric A. Whitsel, Ko Willems van Dijk, Najaf Amin, André G. Uitterlinden, Eric J.G. Sijbrands, Oscar H. Franco, Abbas Dehghan, Tim D. Spector, Josée Dupuis, Marie France Hivert, Jerome I. Rotter, James B. Meigs, James S. Pankow, Joyce B.J. van Meurs, Aaron Isaacs, Dorret I. Boomsma, Jordana T. Bell, Ayşe Demirkan, Cornelia M. van Duijn

^*此作品的通信作者

生物醫學系(含學士班、臨床試驗與評估碩士班)

Erasmus University Rotterdam
University of Oxford
University of Granada
King's College London
Vrije Universiteit Amsterdam
Boston University
Icahn School of Medicine at Mount Sinai
Harvard University
National Institutes of Health
University of Texas Health Science Center at Houston
University of North Carolina at Chapel Hill
Stanford University
German Center for Diabetes Research
German Diabetes Center Düsseldorf
Heinrich Heine University Düsseldorf
University of Alabama at Birmingham
University of Washington
University of Michigan, Ann Arbor
Azienda Sanitaria di Firenze
University of Kentucky
Helmholtz Zentrum München - German Research Center for Environmental Health
Northwestern University
Columbia University
Leiden University
University of Bern
Imperial College London
Université de Sherbrooke
Massachusetts General Hospital
University of California at Los Angeles
Broad Institute
University of Minnesota Twin Cities
Maastricht University
University of Groningen
University of Surrey

研究成果: 期刊稿件 › 文章 › 同行評審

78 引文斯高帕斯（Scopus）

摘要

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.

原文	英語
文章編號	2581
期刊	Nature Communications
卷	10
發行號	1
DOIs	https://doi.org/10.1038/s41467-019-10487-4
出版狀態	已出版 - 01 12 2019

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© 2019, Crown.

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10.1038/s41467-019-10487-4

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Liu, J., Carnero-Montoro, E., van Dongen, J., Lent, S., Nedeljkovic, I., Ligthart, S., Tsai, P. C., Martin, T. C., Mandaviya, P. R., Jansen, R., Peters, M. J., Duijts, L., Jaddoe, V. W. V., Tiemeier, H., Felix, J. F., Willemsen, G., de Geus, E. J. C., Chu, A. Y., Levy, D., ... van Duijn, C. M. (2019). An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis. Nature Communications, 10(1), 文章 2581. https://doi.org/10.1038/s41467-019-10487-4

@article{818d368d14d649109599073ce040b1f0,

title = "An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis",

abstract = "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.",

author = "Jun Liu and Elena Carnero-Montoro and \{van Dongen\}, Jenny and Samantha Lent and Ivana Nedeljkovic and Symen Ligthart and Tsai, \{Pei Chien\} and Martin, \{Tiphaine C.\} and Mandaviya, \{Pooja R.\} and Rick Jansen and Peters, \{Marjolein J.\} and Liesbeth Duijts and Jaddoe, \{Vincent W.V.\} and Henning Tiemeier and Felix, \{Janine F.\} and Gonneke Willemsen and \{de Geus\}, \{Eco J.C.\} and Chu, \{Audrey Y.\} and Daniel Levy and Hwang, \{Shih Jen\} and Jan Bressler and Rahul Gondalia and Salfati, \{Elias L.\} and Christian Herder and Hidalgo, \{Bertha A.\} and Toshiko Tanaka and Moore, \{Ann Zenobia\} and Lemaitre, \{Rozenn N.\} and Jhun, \{Min A.\} and Smith, \{Jennifer A.\} and Nona Sotoodehnia and Stefania Bandinelli and Luigi Ferrucci and Arnett, \{Donna K.\} and Harald Grallert and Assimes, \{Themistocles L.\} and Lifang Hou and Andrea Baccarelli and Whitsel, \{Eric A.\} and \{van Dijk\}, \{Ko Willems\} and Najaf Amin and Uitterlinden, \{Andr{\'e} G.\} and Sijbrands, \{Eric J.G.\} and Franco, \{Oscar H.\} and Abbas Dehghan and Spector, \{Tim D.\} and Jos{\'e}e Dupuis and Hivert, \{Marie France\} and Rotter, \{Jerome I.\} and Meigs, \{James B.\} and Pankow, \{James S.\} and \{van Meurs\}, \{Joyce B.J.\} and Aaron Isaacs and Boomsma, \{Dorret I.\} and Bell, \{Jordana T.\} and Ay{\c s}e Demirkan and \{van Duijn\}, \{Cornelia M.\}",

note = "Publisher Copyright: {\textcopyright} 2019, Crown.",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-10487-4",

language = "英语",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Liu, J, Carnero-Montoro, E, van Dongen, J, Lent, S, Nedeljkovic, I, Ligthart, S, Tsai, PC, Martin, TC, Mandaviya, PR, Jansen, R, Peters, MJ, Duijts, L, Jaddoe, VWV, Tiemeier, H, Felix, JF, Willemsen, G, de Geus, EJC, Chu, AY, Levy, D, Hwang, SJ, Bressler, J, Gondalia, R, Salfati, EL, Herder, C, Hidalgo, BA, Tanaka, T, Moore, AZ, Lemaitre, RN, Jhun, MA, Smith, JA, Sotoodehnia, N, Bandinelli, S, Ferrucci, L, Arnett, DK, Grallert, H, Assimes, TL, Hou, L, Baccarelli, A, Whitsel, EA, van Dijk, KW, Amin, N, Uitterlinden, AG, Sijbrands, EJG, Franco, OH, Dehghan, A, Spector, TD, Dupuis, J, Hivert, MF, Rotter, JI, Meigs, JB, Pankow, JS, van Meurs, JBJ, Isaacs, A, Boomsma, DI, Bell, JT, Demirkan, A & van Duijn, CM 2019, 'An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis', Nature Communications, 卷 10, 編號 1, 2581. https://doi.org/10.1038/s41467-019-10487-4

TY - JOUR

T1 - An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

AU - Liu, Jun

AU - Carnero-Montoro, Elena

AU - van Dongen, Jenny

AU - Lent, Samantha

AU - Nedeljkovic, Ivana

AU - Ligthart, Symen

AU - Tsai, Pei Chien

AU - Martin, Tiphaine C.

AU - Mandaviya, Pooja R.

AU - Jansen, Rick

AU - Peters, Marjolein J.

AU - Duijts, Liesbeth

AU - Jaddoe, Vincent W.V.

AU - Tiemeier, Henning

AU - Felix, Janine F.

AU - Willemsen, Gonneke

AU - de Geus, Eco J.C.

AU - Chu, Audrey Y.

AU - Levy, Daniel

AU - Hwang, Shih Jen

AU - Bressler, Jan

AU - Gondalia, Rahul

AU - Salfati, Elias L.

AU - Herder, Christian

AU - Hidalgo, Bertha A.

AU - Tanaka, Toshiko

AU - Moore, Ann Zenobia

AU - Lemaitre, Rozenn N.

AU - Jhun, Min A.

AU - Smith, Jennifer A.

AU - Sotoodehnia, Nona

AU - Bandinelli, Stefania

AU - Ferrucci, Luigi

AU - Arnett, Donna K.

AU - Grallert, Harald

AU - Assimes, Themistocles L.

AU - Hou, Lifang

AU - Baccarelli, Andrea

AU - Whitsel, Eric A.

AU - van Dijk, Ko Willems

AU - Amin, Najaf

AU - Uitterlinden, André G.

AU - Sijbrands, Eric J.G.

AU - Franco, Oscar H.

AU - Dehghan, Abbas

AU - Spector, Tim D.

AU - Dupuis, Josée

AU - Hivert, Marie France

AU - Rotter, Jerome I.

AU - Meigs, James B.

AU - Pankow, James S.

AU - van Meurs, Joyce B.J.

AU - Isaacs, Aaron

AU - Boomsma, Dorret I.

AU - Bell, Jordana T.

AU - Demirkan, Ayşe

AU - van Duijn, Cornelia M.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85067366036

U2 - 10.1038/s41467-019-10487-4

DO - 10.1038/s41467-019-10487-4

M3 - 文章

C2 - 31197173

AN - SCOPUS:85067366036

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2581

ER -

An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

摘要

文獻附註

UN SDG

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其它文件與鏈接

指紋

引用此