Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci
Posted on 2021-05-01 - 03:27
Abstract Background DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. Methods The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. Results We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. Conclusions We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.
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Breeze, Charles E.; Batorsky, Anna; Lee, Mi Kyeong; Szeto, Mindy D.; Xu, Xiaoguang; McCartney, Daniel L.; et al. (2021). Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5409657.v1
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AUTHORS (42)
CB
Charles E. Breeze
AB
Anna Batorsky
ML
Mi Kyeong Lee
MS
Mindy D. Szeto
XX
Xiaoguang Xu
DM
Daniel L. McCartney
RJ
Rong Jiang
AP
Amit Patki
HK
Holly J. Kramer
JE
James M. Eales
LR
Laura Raffield
LL
Leslie Lange
EL
Ethan Lange
PD
Peter Durda
YL
Yongmei Liu
RT
Russ P. Tracy
DV
David Van Den Berg
KE
Kathryn L. Evans
WK
William E. Kraus
SS
Svati Shah