Meta-analyses identify DNA methylation associated with kidney function and damage

Pascal Schlosser; Adrienne Tin; Pamela R. Matias-garcia; Chris H. L. Thio; Roby Joehanes; Hongbo Liu; Antoine Weihs; Zhi Yu; Anselm Hoppmann; Franziska Grundner-culemann; Josine L. Min; Adebowale A. Adeyemo; Charles Agyemang; Johan Ärnlöv; Nasir A. Aziz; Andrea Baccarelli; Murielle Bochud; Hermann Brenner; Monique M. B. Breteler; Cristian Carmeli; Layal Chaker; John C. Chambers; Shelley A. Cole; Josef Coresh; Tanguy Corre; Adolfo Correa; Simon R. Cox; Niek De Klein; Graciela E. Delgado; Arce Domingo-relloso; Kai-uwe Eckardt; Arif B. Ekici; Karlhans Endlich; Kathryn L. Evans; James S. Floyd; Myriam Fornage; Lude Franke; Eliza Fraszczyk; Xu Gao; Xīn Gào; Mohsen Ghanbari; Sahar Ghasemi; Christian Gieger; Philip Greenland; Megan L. Grove; Sarah E. Harris; Gibran Hemani; Peter Henneman; Christian Herder; Steve Horvath; Lifang Hou; Mikko A. Hurme; Shih-jen Hwang; Marjo-riitta Jarvelin; Sharon L. R. Kardia; Silva Kasela; Marcus E. Kleber; Wolfgang Koenig; Jaspal S. Kooner; Holly Kramer; Florian Kronenberg; Brigitte Kühnel; Terho Lehtimäki; Lars Lind; Dan Liu; Yongmei Liu; Donald M. Lloyd-jones; Kurt Lohman; Stefan Lorkowski; Ake T. Lu; Riccardo E. Marioni; Winfried März; Daniel L. Mccartney; Karlijn A. C. Meeks; Lili Milani; Pashupati P. Mishra; Matthias Nauck; Ana Navas-acien; Christoph Nowak; Annette Peters; Holger Prokisch; Bruce M. Psaty; Olli T. Raitakari; Scott M. Ratliff; Alex P. Reiner; Sylvia E. Rosas; Ben Schöttker; Joel Schwartz; Sanaz Sedaghat; Jennifer A. Smith; Nona Sotoodehnia; Hannah R. Stocker; Silvia Stringhini; Johan Sundström; Brenton R. Swenson; Maria Tellez-plaza; Joyce B. J. Van Meurs; Jana V. Van Vliet-ostaptchouk; Andrea Venema; Niek Verweij; Rosie M. Walker; Matthias Wielscher; Juliane Winkelmann; Bruce H. R. Wolffenbuttel; Wei Zhao; Yinan Zheng; Lili Milani; Marie Loh; Harold Snieder; Daniel Levy; Melanie Waldenberger; Katalin Susztak; Anna Köttgen; Alexander Teumer

doi:10.1038/s41467-021-27234-3

Meta-analyses identify DNA methylation associated with kidney function and damage

Pascal Schlosser, Adrienne Tin, Pamela R. Matias-garcia, Chris H. L. Thio, Roby Joehanes, Hongbo Liu, Antoine Weihs, Zhi Yu, Anselm Hoppmann, Franziska Grundner-culemann, Josine L. Min, Adebowale A. Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A. Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Monique M. B. Breteler, Cristian CarmeliLayal Chaker, John C. Chambers, Shelley A. Cole, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R. Cox, Niek De Klein, Graciela E. Delgado, Arce Domingo-relloso, Kai-uwe Eckardt, Arif B. Ekici, Karlhans Endlich, Kathryn L. Evans, James S. Floyd, Myriam Fornage, Lude Franke, Eliza Fraszczyk, Xu Gao, Xīn Gào, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L. Grove, Sarah E. Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A. Hurme, Shih-jen Hwang, Marjo-riitta Jarvelin, Sharon L. R. Kardia, Silva Kasela, Marcus E. Kleber, Wolfgang Koenig, Jaspal S. Kooner, Holly Kramer, Florian Kronenberg, Brigitte Kühnel, Terho Lehtimäki, Lars Lind, Dan Liu, Yongmei Liu, Donald M. Lloyd-jones, Kurt Lohman, Stefan Lorkowski, Ake T. Lu, Riccardo E. Marioni, Winfried März, Daniel L. Mccartney, Karlijn A. C. Meeks, Lili Milani, Pashupati P. Mishra, Matthias Nauck, Ana Navas-acien, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M. Psaty, Olli T. Raitakari, Scott M. Ratliff, Alex P. Reiner, Sylvia E. Rosas, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A. Smith, Nona Sotoodehnia, Hannah R. Stocker, Silvia Stringhini, Johan Sundström, Brenton R. Swenson, Maria Tellez-plaza, Joyce B. J. Van Meurs, Jana V. Van Vliet-ostaptchouk, Andrea Venema, Niek Verweij, Rosie M. Walker, Matthias Wielscher, Juliane Winkelmann, Bruce H. R. Wolffenbuttel, Wei Zhao, Yinan Zheng, Lili Milani, Marie Loh, Harold Snieder, Daniel Levy, Melanie Waldenberger, Katalin Susztak, Anna Köttgen, Alexander Teumer

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

Original language	English
Article number	7174
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27234-3
Publication status	Published - 9 Dec 2021

Keywords / Materials (for Non-textual outputs)

chronic kidney disease
DNA methylation
epidemiology
translational research

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SchlosserEtAlNC2021Meta-analysesIdentifyFinal published version, 3.59 MBLicence: Creative Commons: Attribution (CC-BY)

https://doi.org/10.1038/s41467-021-27234-3Licence: Creative Commons: Attribution (CC-BY)

Cite this

Schlosser, P., Tin, A., Matias-garcia, P. R., Thio, C. H. L., Joehanes, R., Liu, H., Weihs, A., Yu, Z., Hoppmann, A., Grundner-culemann, F., Min, J. L., Adeyemo, A. A., Agyemang, C., Ärnlöv, J., Aziz, N. A., Baccarelli, A., Bochud, M., Brenner, H., Breteler, M. M. B., ... Teumer, A. (2021). Meta-analyses identify DNA methylation associated with kidney function and damage. Nature Communications, 12(1), Article 7174. https://doi.org/10.1038/s41467-021-27234-3

@article{99c5bdd56be14e5f9b59fca66c14567b,

title = "Meta-analyses identify DNA methylation associated with kidney function and damage",

abstract = "Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.",

keywords = "chronic kidney disease, DNA methylation, epidemiology, translational research",

author = "Pascal Schlosser and Adrienne Tin and Matias-garcia, {Pamela R.} and Thio, {Chris H. L.} and Roby Joehanes and Hongbo Liu and Antoine Weihs and Zhi Yu and Anselm Hoppmann and Franziska Grundner-culemann and Min, {Josine L.} and Adeyemo, {Adebowale A.} and Charles Agyemang and Johan {\"A}rnl{\"o}v and Aziz, {Nasir A.} and Andrea Baccarelli and Murielle Bochud and Hermann Brenner and Breteler, {Monique M. B.} and Cristian Carmeli and Layal Chaker and Chambers, {John C.} and Cole, {Shelley A.} and Josef Coresh and Tanguy Corre and Adolfo Correa and Cox, {Simon R.} and {De Klein}, Niek and Delgado, {Graciela E.} and Arce Domingo-relloso and Kai-uwe Eckardt and Ekici, {Arif B.} and Karlhans Endlich and Evans, {Kathryn L.} and Floyd, {James S.} and Myriam Fornage and Lude Franke and Eliza Fraszczyk and Xu Gao and Xīn G{\`a}o and Mohsen Ghanbari and Sahar Ghasemi and Christian Gieger and Philip Greenland and Grove, {Megan L.} and Harris, {Sarah E.} and Gibran Hemani and Peter Henneman and Christian Herder and Steve Horvath and Lifang Hou and Hurme, {Mikko A.} and Shih-jen Hwang and Marjo-riitta Jarvelin and Kardia, {Sharon L. R.} and Silva Kasela and Kleber, {Marcus E.} and Wolfgang Koenig and Kooner, {Jaspal S.} and Holly Kramer and Florian Kronenberg and Brigitte K{\"u}hnel and Terho Lehtim{\"a}ki and Lars Lind and Dan Liu and Yongmei Liu and Lloyd-jones, {Donald M.} and Kurt Lohman and Stefan Lorkowski and Lu, {Ake T.} and Marioni, {Riccardo E.} and Winfried M{\"a}rz and Mccartney, {Daniel L.} and Meeks, {Karlijn A. C.} and Lili Milani and Mishra, {Pashupati P.} and Matthias Nauck and Ana Navas-acien and Christoph Nowak and Annette Peters and Holger Prokisch and Psaty, {Bruce M.} and Raitakari, {Olli T.} and Ratliff, {Scott M.} and Reiner, {Alex P.} and Rosas, {Sylvia E.} and Ben Sch{\"o}ttker and Joel Schwartz and Sanaz Sedaghat and Smith, {Jennifer A.} and Nona Sotoodehnia and Stocker, {Hannah R.} and Silvia Stringhini and Johan Sundstr{\"o}m and Swenson, {Brenton R.} and Maria Tellez-plaza and {Van Meurs}, {Joyce B. J.} and {Van Vliet-ostaptchouk}, {Jana V.} and Andrea Venema and Niek Verweij and Walker, {Rosie M.} and Matthias Wielscher and Juliane Winkelmann and Wolffenbuttel, {Bruce H. R.} and Wei Zhao and Yinan Zheng and Lili Milani and Marie Loh and Harold Snieder and Daniel Levy and Melanie Waldenberger and Katalin Susztak and Anna K{\"o}ttgen and Alexander Teumer",

year = "2021",

month = dec,

day = "9",

doi = "10.1038/s41467-021-27234-3",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Schlosser, P, Tin, A, Matias-garcia, PR, Thio, CHL, Joehanes, R, Liu, H, Weihs, A, Yu, Z, Hoppmann, A, Grundner-culemann, F, Min, JL, Adeyemo, AA, Agyemang, C, Ärnlöv, J, Aziz, NA, Baccarelli, A, Bochud, M, Brenner, H, Breteler, MMB, Carmeli, C, Chaker, L, Chambers, JC, Cole, SA, Coresh, J, Corre, T, Correa, A, Cox, SR, De Klein, N, Delgado, GE, Domingo-relloso, A, Eckardt, K, Ekici, AB, Endlich, K, Evans, KL, Floyd, JS, Fornage, M, Franke, L, Fraszczyk, E, Gao, X, Gào, X, Ghanbari, M, Ghasemi, S, Gieger, C, Greenland, P, Grove, ML, Harris, SE, Hemani, G, Henneman, P, Herder, C, Horvath, S, Hou, L, Hurme, MA, Hwang, S, Jarvelin, M, Kardia, SLR, Kasela, S, Kleber, ME, Koenig, W, Kooner, JS, Kramer, H, Kronenberg, F, Kühnel, B, Lehtimäki, T, Lind, L, Liu, D, Liu, Y, Lloyd-jones, DM, Lohman, K, Lorkowski, S, Lu, AT, Marioni, RE, März, W, Mccartney, DL, Meeks, KAC, Milani, L, Mishra, PP, Nauck, M, Navas-acien, A, Nowak, C, Peters, A, Prokisch, H, Psaty, BM, Raitakari, OT, Ratliff, SM, Reiner, AP, Rosas, SE, Schöttker, B, Schwartz, J, Sedaghat, S, Smith, JA, Sotoodehnia, N, Stocker, HR, Stringhini, S, Sundström, J, Swenson, BR, Tellez-plaza, M, Van Meurs, JBJ, Van Vliet-ostaptchouk, JV, Venema, A, Verweij, N, Walker, RM, Wielscher, M, Winkelmann, J, Wolffenbuttel, BHR, Zhao, W, Zheng, Y, Milani, L, Loh, M, Snieder, H, Levy, D, Waldenberger, M, Susztak, K, Köttgen, A & Teumer, A 2021, 'Meta-analyses identify DNA methylation associated with kidney function and damage', Nature Communications, vol. 12, no. 1, 7174. https://doi.org/10.1038/s41467-021-27234-3

TY - JOUR

T1 - Meta-analyses identify DNA methylation associated with kidney function and damage

AU - Schlosser, Pascal

AU - Tin, Adrienne

AU - Matias-garcia, Pamela R.

AU - Thio, Chris H. L.

AU - Joehanes, Roby

AU - Liu, Hongbo

AU - Weihs, Antoine

AU - Yu, Zhi

AU - Hoppmann, Anselm

AU - Grundner-culemann, Franziska

AU - Min, Josine L.

AU - Adeyemo, Adebowale A.

AU - Agyemang, Charles

AU - Ärnlöv, Johan

AU - Aziz, Nasir A.

AU - Baccarelli, Andrea

AU - Bochud, Murielle

AU - Brenner, Hermann

AU - Breteler, Monique M. B.

AU - Carmeli, Cristian

AU - Chaker, Layal

AU - Chambers, John C.

AU - Cole, Shelley A.

AU - Coresh, Josef

AU - Corre, Tanguy

AU - Correa, Adolfo

AU - Cox, Simon R.

AU - De Klein, Niek

AU - Delgado, Graciela E.

AU - Domingo-relloso, Arce

AU - Eckardt, Kai-uwe

AU - Ekici, Arif B.

AU - Endlich, Karlhans

AU - Evans, Kathryn L.

AU - Floyd, James S.

AU - Fornage, Myriam

AU - Franke, Lude

AU - Fraszczyk, Eliza

AU - Gao, Xu

AU - Gào, Xīn

AU - Ghanbari, Mohsen

AU - Ghasemi, Sahar

AU - Gieger, Christian

AU - Greenland, Philip

AU - Grove, Megan L.

AU - Harris, Sarah E.

AU - Hemani, Gibran

AU - Henneman, Peter

AU - Herder, Christian

AU - Horvath, Steve

AU - Hou, Lifang

AU - Hurme, Mikko A.

AU - Hwang, Shih-jen

AU - Jarvelin, Marjo-riitta

AU - Kardia, Sharon L. R.

AU - Kasela, Silva

AU - Kleber, Marcus E.

AU - Koenig, Wolfgang

AU - Kooner, Jaspal S.

AU - Kramer, Holly

AU - Kronenberg, Florian

AU - Kühnel, Brigitte

AU - Lehtimäki, Terho

AU - Lind, Lars

AU - Liu, Dan

AU - Liu, Yongmei

AU - Lloyd-jones, Donald M.

AU - Lohman, Kurt

AU - Lorkowski, Stefan

AU - Lu, Ake T.

AU - Marioni, Riccardo E.

AU - März, Winfried

AU - Mccartney, Daniel L.

AU - Meeks, Karlijn A. C.

AU - Milani, Lili

AU - Mishra, Pashupati P.

AU - Nauck, Matthias

AU - Navas-acien, Ana

AU - Nowak, Christoph

AU - Peters, Annette

AU - Prokisch, Holger

AU - Psaty, Bruce M.

AU - Raitakari, Olli T.

AU - Ratliff, Scott M.

AU - Reiner, Alex P.

AU - Rosas, Sylvia E.

AU - Schöttker, Ben

AU - Schwartz, Joel

AU - Sedaghat, Sanaz

AU - Smith, Jennifer A.

AU - Sotoodehnia, Nona

AU - Stocker, Hannah R.

AU - Stringhini, Silvia

AU - Sundström, Johan

AU - Swenson, Brenton R.

AU - Tellez-plaza, Maria

AU - Van Meurs, Joyce B. J.

AU - Van Vliet-ostaptchouk, Jana V.

AU - Venema, Andrea

AU - Verweij, Niek

AU - Walker, Rosie M.

AU - Wielscher, Matthias

AU - Winkelmann, Juliane

AU - Wolffenbuttel, Bruce H. R.

AU - Zhao, Wei

AU - Zheng, Yinan

AU - Milani, Lili

AU - Loh, Marie

AU - Snieder, Harold

AU - Levy, Daniel

AU - Waldenberger, Melanie

AU - Susztak, Katalin

AU - Köttgen, Anna

AU - Teumer, Alexander

PY - 2021/12/9

Y1 - 2021/12/9

N2 - Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

AB - Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

KW - chronic kidney disease

KW - DNA methylation

KW - epidemiology

KW - translational research

UR - https://ckdgen.imbi.uni-freiburg.de/

UR - https://github.com/genepi-freiburg/ckdgen-pheno-ewas

U2 - 10.1038/s41467-021-27234-3

DO - 10.1038/s41467-021-27234-3

M3 - Article

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7174

ER -

Meta-analyses identify DNA methylation associated with kidney function and damage

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Keywords / Materials (for Non-textual outputs)

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