Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter syndrome

SUMMARY Klinefelter syndrome (KS) (47 XXY) is a common sex‐chromosome aneuploidy with an estimated prevalence of one in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary X chromosome; systematic investigations of the epigenome have been limited. We obtained genome‐wide DNA methylation data from peripheral blood using the Illumina HumanMethylation450K platform in 5 KS (47 XXY) versus 102 male (46 XY) and 113 female (46 XX) control subjects participating in the COPDGene Study. Empirical Bayes‐mediated models were used to test for differential methylation by KS status. CpG sites with a false‐discovery rate