Shared genetic control of expression and methylation in peripheral blood

Konstantin Shakhbazov, Joseph E Powell, Gibran Hemani, Anjali K Henders, Nicholas G Martin, Peter M Visscher, Grant W Montgomery, Allan F McRae

Research output: Contribution to journalArticle (Academic Journal)peer-review

8 Citations (Scopus)
140 Downloads (Pure)


Expression QTLs and epigenetic marks are often employed to provide an insight into the possible biological mechanisms behind GWAS hits. A substantial proportion of the variation in gene expression and DNA methylation is known to be under genetic control. We address the proportion of genetic control that is shared between these two genomic features.

An exhaustive search for pairwise phenotypic correlations between gene expression and DNA methylation in samples from human blood (n = 610) was performed. Of the 5 × 109 possible pairwise tests, 0.36 % passed Bonferroni corrected p-value cutoff of 9.9 × 10-12. We determined that the correlation structure between probe pairs was largely due to blood cell type specificity of the expression and methylation probes. Upon adjustment of the expression and methylation values for observed blood cellular composition (n = 422), the number of probe pairs which survived Bonferroni correction reduced by more than 5400 fold. Of the 614 correlated probe pairs located on the same chromosome, 75 % share at least one methylation and expression QTL at nominal 10-5 p-value cutoff. Those probe pairs are located within 1Mbp window from each other and have a mean of absolute value of genetic correlation equal to 0.69, further demonstrating the high degree of shared genetic control.

Overall, this study demonstrates notable genetic covariance between DNA methylation and gene expression and reaffirms the importance of correcting for cell-counts in studies on non-homogeneous tissues.
Original languageEnglish
Article number278
Number of pages13
JournalBMC Genomics
Publication statusPublished - 6 Apr 2016


  • Gene expression
  • DNA methylation
  • Genetic correlation


Dive into the research topics of 'Shared genetic control of expression and methylation in peripheral blood'. Together they form a unique fingerprint.

Cite this