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Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci
- Source :
- 2021, ' Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci ', Genome Medicine, vol. 13, no. 1, 74 . https://doi.org/10.1186/s13073-021-00877-z, Genome medicine, vol 13, iss 1, Genome Medicine, Vol 13, Iss 1, Pp 1-16 (2021), Genome Medicine, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium & TOPMed MESA Multi-Omics Working Group 2021, ' Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci ', Genome Medicine, vol. 13, no. 1, 74, pp. 74 . https://doi.org/10.1186/s13073-021-00877-z
- Publication Year :
- 2021
-
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.
- Subjects :
- Epigenomics
Kidney Disease
Kidney development
QH426-470
Kidney
Kidney Function Tests
Epigenesis, Genetic
0302 clinical medicine
Genetics (clinical)
Regulation of gene expression
Genetics
0303 health sciences
DNA methylation
Epigenetic
3. Good health
Phenotype
030220 oncology & carcinogenesis
Medicine
Molecular Medicine
Glomerular Filtration Rate
Population
Quantitative Trait Loci
Clinical Sciences
Renal and urogenital
Context (language use)
Biology
Quantitative Trait
03 medical and health sciences
Quantitative Trait, Heritable
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Kidney function
Genetic
Humans
Epigenetics
Heritable
Molecular Biology
030304 developmental biology
Research
Human Genome
Racial Groups
Genetic Variation
dNaM
Epigenome
Gene regulation
Genetics, Population
Gene Expression Regulation
TOPMed MESA Multi-Omics Working Group
CpG Islands
Epigenesis
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- 2021, ' Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci ', Genome Medicine, vol. 13, no. 1, 74 . https://doi.org/10.1186/s13073-021-00877-z, Genome medicine, vol 13, iss 1, Genome Medicine, Vol 13, Iss 1, Pp 1-16 (2021), Genome Medicine, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium & TOPMed MESA Multi-Omics Working Group 2021, ' Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci ', Genome Medicine, vol. 13, no. 1, 74, pp. 74 . https://doi.org/10.1186/s13073-021-00877-z
- Accession number :
- edsair.doi.dedup.....128c672f4077cb7aa7ff1ee829272450