A correlation map of genome-wide DNA methylation patterns between paired human brain and buccal samples

Epigenome-wide association studies (EWAS) assessing the link between DNA methylation (DNAm) and phenotypes related to structural brain measures, cognitive function, and neurodegenerative diseases are becoming increasingly more popular. Due to the inaccessibility of brain tissue in humans, several studies use peripheral tissues such as blood, buccal swabs, and saliva as surrogates. To aid the functional interpretation of EWAS findings in such settings, there is a need to assess the correlation of DNAm variability across tissues in the same individuals. In this study, we performed a correlation analysis between DNAm data of a total of n = 120 matched post-mortem buccal and prefrontal cortex samples. We identified nearly 25,000 (3% of approximately 730,000) cytosine-phosphate-guanine (CpG) sites showing significant (false discovery rate q < 0.05) correlations between buccal and PFC samples. Correlated CpG sites showed a preponderance to being located in promoter regions and showed a significant enrichment of being determined by genetic factors, i.e. methylation quantitative trait loci (mQTL), based on buccal and dorsolateral prefrontal cortex mQTL databases. Our novel buccal-brain DNAm correlation map will provide a valuable resource for future EWAS using buccal samples for studying DNAm effects on phenotypes relating to the brain. All correlation results are made freely available to the public online.

Automated summary

Epigenome-wide association studies (EWAS) have gained popularity in assessing the connection between DNA methylation (DNAm) and phenotypes related to brain measures, cognitive function, and neurodegenerative diseases. This study used peripheral tissues such as blood, buccal swabs, and saliva as surrogates for brain tissue, and identified significant correlations of DNAm variability between buccal and prefrontal cortex samples. The correlated CpG sites were mostly located in promoter regions and were influenced by genetic factors.