Epigenome-wide cross-tissue correlation of human bone and blood DNA methylation - can blood be used as a surrogate for bone?

Epigenetics : Official Journal of the DNA Methylation Society
Parvaneh EbrahimiKristina E Akesson

Abstract

Difficulty in obtaining bone tissue is an obstacle to studying epigenetics to understand gene-environment interactions, and their role in disease pathogenesis. Blood is an obvious alternative and in this proof of principle study, our aim was to systematically investigate whether blood is a viable surrogate for bone. We measured epigenome-wide DNA methylation at 850 K CpG sites in matched trabecular bone and peripheral blood collected from the same patients at the same time-point (n = 12 women; 66-85y), to investigate the between-tissue correspondence. What constituted a CpG site with corresponding methylation in both tissues was stringently defined. Only sites highly correlated (r2 > 0.74; FDR q-value <0.05) and at least 80% similarity in methylation level (Δβ <0.2) between paired samples were retained. In total, 28,549 CpG sites were similarly methylated in bone and blood. Between 33% and 49% of loci associated with bone phenotypes through GWAS were represented among these sites, and major pathways relevant to bone regulation were enriched. The results from this study indicate that blood can mirror the bone methylome and capture sites related to bone regulation. This study shows that in principal, peripheral blood is a feasibl...Continue Reading

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Methods Mentioned

BETA
biopsies
chips
chip
MDS
PCA

Software Mentioned

R package Rfast
ComBat
surrogate variable analysis ( SVA )
Bioconductor
Limma
R
Minfi
missMethyl R package

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