Diversity and inclusion are important components of our modern society, and epigenomics is no exception. To build on our knowledge of ethnic differences and similarities, an inclusive epigenome-wide association study (EWAS) of kidney function has come forth to filter the hits.
A group led by Charles Breeze (National Cancer Institute) and Nora Franceschini (University of North Carolina) conducted a DNA methylation (DNAm) EWAS of kidney function in ethnically diverse and uniform populations. Their discovery cohort included a total of 5428 participants from multi-ethnic studies of which 2879 are African American (AA), 1737 are European American (EA), and 812 are Hispanic/Latino (H/L). Then, they examined a replication cohort comprised of 8109 participants (EA: 7349, AA: 760). They determined the association between whole-blood DNAm and estimated glomerular filtration rate (eGFR), a standard method for assessing kidney function, since decreased eGFR is common amongst AA and H/L. Get a load of the insights their eFORGE analyses led to:
- In the discovery cohort, 93 differentially methylated positions (DMPs) associate with eGFR
- 78 are trans-ethnic, 23 are specific to AA, 5 to EA and 5 to H/L
- 6 of the DMPs had been previously associated to eGFR, which supports the validity of their analytical approach
- They replicated 13 out of the 78 trans-ethnic DMPs and 1 out of the 23 AA-specific DMPs
- Importantly, all but one of the replicated trans-ethnic DMPs are newly identified in this study
- One of the replicated trans-ethnic DMPs (cg11789371) is located in an intron of HSP90AA1, which codes for a protein that helps defend kidney tissue from inflammation, ischemia and oxidative stress
- This gene is involved in regulating eGFR and is a potential therapeutic target for kidney disease
- The CpG site overlaps with a DNase I hypersensitive site (DHS) and H3K27ac peak in kidney cells, and is the target of a cis-methylation quantitative trait locus (cis-meQTL), a SNP upstream in another intron of HSP90AA1
- Importantly, eGFR-linked DMPs present enrichment for eGFR genome-wide association study (GWAS) genomic variant-associated DNAm, pointing to a potential convergence between eGFR EWAS and GWAS
- eGFR-linked DMPs also show enrichment for kidney-specific DHSs as well as for motifs of transcription factors involved in pathways associated with kidney development, for example OSR1/2, TBX1 and PAX2
First author Charles Breeze comments, “This study shows that analyzing epigenomic data from diverse backgrounds is both informative and valuable for understanding kidney function.” Nora Franceschini importantly points out that “research can only work for all of us if it includes all of us.”
Filter through all the details in Genome Medicine, April 2021.