Skip to main content
Journal cover image

Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci.

Publication ,  Journal Article
Breeze, CE; Batorsky, A; Lee, MK; Szeto, MD; Xu, X; McCartney, DL; Jiang, R; Patki, A; Kramer, HJ; Eales, JM; Raffield, L; Lange, L; Lange, E ...
Published in: Genome medicine
April 2021

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.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.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.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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Genome medicine

DOI

EISSN

1756-994X

ISSN

1756-994X

Publication Date

April 2021

Volume

13

Issue

1

Start / End Page

74

Related Subject Headings

  • Racial Groups
  • Quantitative Trait, Heritable
  • Quantitative Trait Loci
  • Phenotype
  • Kidney Function Tests
  • Kidney
  • Humans
  • Glomerular Filtration Rate
  • Genome-Wide Association Study
  • Genetics, Population
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Breeze, C. E., Batorsky, A., Lee, M. K., Szeto, M. D., Xu, X., McCartney, D. L., … Franceschini, N. (2021). Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci. Genome Medicine, 13(1), 74. https://doi.org/10.1186/s13073-021-00877-z
Breeze, Charles E., Anna Batorsky, Mi Kyeong Lee, Mindy D. Szeto, Xiaoguang Xu, Daniel L. McCartney, Rong Jiang, et al. “Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci.Genome Medicine 13, no. 1 (April 2021): 74. https://doi.org/10.1186/s13073-021-00877-z.
Breeze CE, Batorsky A, Lee MK, Szeto MD, Xu X, McCartney DL, et al. Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci. Genome medicine. 2021 Apr;13(1):74.
Breeze, Charles E., et al. “Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci.Genome Medicine, vol. 13, no. 1, Apr. 2021, p. 74. Epmc, doi:10.1186/s13073-021-00877-z.
Breeze CE, Batorsky A, Lee MK, Szeto MD, Xu X, McCartney DL, Jiang R, Patki A, Kramer HJ, Eales JM, Raffield L, Lange L, Lange E, Durda P, Liu Y, Tracy RP, Van Den Berg D, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed MESA Multi-Omics Working Group, Evans KL, Kraus WE, Shah S, Tiwari HK, Hou L, Whitsel EA, Jiang X, Charchar FJ, Baccarelli AA, Rich SS, Morris AP, Irvin MR, Arnett DK, Hauser ER, Rotter JI, Correa A, Hayward C, Horvath S, Marioni RE, Tomaszewski M, Beck S, Berndt SI, London SJ, Mychaleckyj JC, Franceschini N. Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci. Genome medicine. 2021 Apr;13(1):74.
Journal cover image

Published In

Genome medicine

DOI

EISSN

1756-994X

ISSN

1756-994X

Publication Date

April 2021

Volume

13

Issue

1

Start / End Page

74

Related Subject Headings

  • Racial Groups
  • Quantitative Trait, Heritable
  • Quantitative Trait Loci
  • Phenotype
  • Kidney Function Tests
  • Kidney
  • Humans
  • Glomerular Filtration Rate
  • Genome-Wide Association Study
  • Genetics, Population