Recent studies highlighted that DNA or histone biochemical modifications, called epigenetic marks, influence adaptation and production traits. However, whether the epigenetic variations are under a genetic determinism or not remains unknown. To answer this question, we have considered DNA global methylation rate (DGMR) as a new phenotype in sheep. DGMR was obtained by LUminometric Methylation Analysis (LUMA) using a pyrosequencing approach and its variability was explored in blood cells and other various tissues, within breed and between breeds. Thus, 30 lambs from 2 sheep breeds (Romane and Martinik Black Belly; 16 males and 14 females) were bred simultaneously to share a common environment. At the age of 5 mo, they were slaughtered and 17 tissues per animal were collected. Concerning the non-reproductive tissues, the sex, breed and tissue effects and their interactions were tested. The tissue effect was highly significant (P < 0.0001), the sex effect was only significant for the pancreas and the kidney cortex (sex*tissue interaction P value = 0.03), whereas the breed effect was never significant. Concerning the reproductive tissues, the breed and tissue effects were significant (P = 0.02 and P < 0.0001, respectively), the DGMR in Martinik Black Belly being higher than in Romane, whatever the tissue. The correlations between the DGMR measured in blood cells and other tissues were low or not significant, indicating that blood DGMR would not be a predictor of the DGMR of tissue less accessible. The proof of concept of the existence of a genetic determinism of DGMR considered as a quantitative trait was obtained through LUMA measurement of 940 DNA blood samples from Romane lambs genotyped on the 50K SNP chip. Blood DGMR was variable between animals with an average of 70.7 ± 6.0%. Among the tested effects, the sex and the ram effects were significant. Blood DGMR was heritable (0.20 ± 0.05) and joint analyses combining linkage disequilibrium and linkage revealed 2 main genomic regions influencing this new phenotype. Such results indicate that blood DGMR could be used in genetic selection, but before, further analyses are in progress to investigate relationship between blood DGMR and productive or adaptive traits.