TY - JOUR
T1 - Meta-analyses identify DNA methylation associated with kidney function and damage
AU - Estonian Biobank Research Team
AU - Genetics of DNA Methylation Consortium
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 - van Vliet-Ostaptchouk, Jana V.
AU - Verweij, Niek
AU - Wolffenbuttel, Bruce H.R.
AU - Zhao, Wei
AU - Snieder, Harold
N1 - Funding Information:
Johan Ärnlöv has served on advisory boards for AstraZeneca and Boehringer Ingelheim, and have received lecturing fees from AstraZeneca and Novartis, all unrelated to the present project. Josef Coresh received grants from NIH and consultant to healthy.io. James S. Floyd has consulted from Shionogi Inc. Christian Herder reports personal fees from Sanofi and Lilly and grant support from Sanofi outside the submitted work. Marcus Kleber is employed with SYNLAB Holding Deutschland GmbH. Wolfgang Koenig reports personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, DalCor, Kowa, Amgen, Corvidia, Daichii-Sankyo, Genentech, Novo Nordisk, Omeicos, Esperion, Berlin-Chemie, Sanofi, and Bristol-Myers Squibb and grants and non-financial support from Abbott, Roche Diagnostics, Beckmann, and Singulex outside the submitted work. S. Lorkowski reports grants and personal fees from Akcea Therapeutics Germany, and personal fees from amedes, AMGEN, Berlin-Chemie, Boehringer Ingelheim Pharma, Daiichi Sankyo, Lilly Deutschland, MSD Sharp & Dohme, Novo Nordisk Pharma, Roche Pharma, Sanofi-Aventis, Synlab Holding Deutschland, Unilever and Upfield, all outside the submitted work. Riccardo E. Marioni has received payment from Illumina for presentations. Winfried März reports grants from Siemens Healthineers, grants and personal fees from Aegerion Pharmaceuticals, grants and personal fees from AMGEN, grants from Astrazeneca, grants and personal fees from Sanofi, grants and personal fees from Alexion Pharmaceuticals, grants and personal fees from BASF, grants and personal fees from Abbott Diagnostics, grants and personal fees from Numares AG, grants and personal fees from Berlin-Chemie, grants and personal fees from Akzea Therapeutics, grants from Bayer Vital GmbH, grants from bestbion dx GmbH, grants from Boehringer Ingelheim Pharma GmbH Co KG, grants from Immundiagnostik GmbH, grants from Merck Chemicals GmbH, grants from MSD Sharp and Dohme GmbH, grants from Novartis Pharma GmbH, grants from Olink Proteomics, other from Synlab Holding Deutschland GmbH, all outside the submitted work. Bruce M. Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Sylvia Rosas receives research funding through her institution for clinical trials from Bayer and Astra Zeneca. She has participated in advisory boards for Reata and Relypsa. Johan Sundström reports ownership in companies providing services to Itrim, Amgen, Janssen, Novo Nordisk, Eli Lilly, Boehringer, Bayer, Pfizer and AstraZeneca, outside the submitted work. Niek Verweij is currently employee of Regeneron Genetics Center. All other authors report no competing interests.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
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.
U2 - 10.1038/s41467-021-27234-3
DO - 10.1038/s41467-021-27234-3
M3 - Article
C2 - 34887417
AN - SCOPUS:85120946524
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
M1 - 7174
ER -