Leukocyte DNA methylation in Alzheimer´s disease associated genes: replication of findings from neuronal cells

Differences in gene-wide DNA methylation of the Alzheimer’s disease (AD)-associated genes <i>BIN1, HLA-DRB5, SORL1, SLC24A4</i>, and <i>ABCA7</i> are reported to be associated with AD in post-mortem brain samples. We investigated whether the same associations could be found in leukocytes collected pre-mortem. Using cohort data of 544 Swedish twins (204 dementia diagnoses), we replicated the findings in <i>HLA-DRB5</i> and <i>SLC24A4</i> at <i>P</i> &lt; 0.05. However, co-twin control analyses indicated that the associations were partly explained by familial confounding. Thus, DNA methylation differences in <i>HLA-DRB5</i> and <i>SLC24A4</i> are present in both neuronal cells and leukocytes, and not fully explained familial factors.