This 2023 human study investigated associations of peripheral and brain epigenetic measurements:
“Evaluating DNA methylation of brain tissue is challenging owing to the issue of tissue specificity. Consequently, peripheral surrogate tissues are used, resulting in limited progress compared with other epigenetic studies.
Averaging data for each CpG across individuals, saliva–brain correlation (r = 0.90) was higher than that for blood–brain (r = 0.87) and buccal–brain (r = 0.88) comparisons. Among individual CpGs, blood had the highest proportion of CpGs correlated to the brain at nominally significant levels (19.0%), followed by saliva (14.4%) and buccal (9.8%). However, cross-database correlations of correlation coefficients revealed relatively low brain vs. blood: r = 0.27, saliva: r = 0.18, and buccal: r = 0.24.
The majority of methylation in the brain is most likely not synchronized with methylation in the periphery. Despite this, variable CpGs that correlate in the brain and periphery, although in small numbers, may have biological relevance, and could be useful for inferring brain methylation from peripheral tissues. This study has six major limitations.”
https://www.nature.com/articles/s41398-023-02370-0 “Cross-tissue correlations of genome-wide DNA methylation in Japanese live human brain and blood, saliva, and buccal epithelial tissues”
Real science is messy. Hypotheses are experimentally reevaluated many, many times under varying conditions. I skip over studies where researchers don’t provide meaningful limitation clauses.