Title: Aberrant DNA Methylation of Imprint Control Regions and Alzheimer's Disease in Humans
Abstract:Alzheimer’s disease (AD) is the sixth leading cause of death in the United States. The prevalence is twice as high in non-Hispanic Blacks (NHBs) as in non-Hispanic Whites (NHWs). The objective of this study was to determine if aberrant methylation at imprint control regions (ICRs) in NHBs and NHWs is associated with AD. Differentially methylated regions (DMRs) were identified using whole-genome bisulfite sequencing of DNA derived from brain tissue of 9 AD cases (5 NHBs and 4 NHWs) and 8 controls (4 NHBs and 4 NHWs). We identified 120 DMRs located within regions previously defined in the human imprintome as putative ICRs. We identified 79 ICRs that are differentially methylated between NHB AD and controls (p < 0.05) and 27 ICRs that are differentially methylated between NHW AD and controls (p < 0.05). While small sample size limits inference, these findings suggest that early-established DNA methylation of regions regulating genomic imprinting contributes to AD risk, and risk may vary by lived experiences of NHB and NHW.
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