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 - Harris, Sarah E.
AU - Hemani, Gibran
AU - Henneman, Peter
AU - Herder, Christian
AU - Winkelmann, Juliane
N1 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85120946524&partnerID=8YFLogxK
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
IS - 1
M1 - 7174
ER -
