TY - JOUR T1 - Epigenome-wide association study of Alzheimer's disease replicates 22 differentially methylated positions and 30 differentially methylated regions. AU - Li,Qingqin S, AU - Sun,Yu, AU - Wang,Tania, Y1 - 2020/10/17/ PY - 2020/06/02/received PY - 2020/10/07/accepted PY - 2020/10/18/entrez PY - 2020/10/19/pubmed PY - 2021/10/21/medline KW - DMP KW - DMR KW - EWAS KW - Epigenetics SP - 149 EP - 149 JF - Clinical epigenetics JO - Clin Epigenetics VL - 12 IS - 1 N2 - BACKGROUND: Growing evidence shows that epigenetic modifications play a role in Alzheimer's disease (AD). We performed an epigenome-wide association study (EWAS) to evaluate the DNA methylation differences using postmortem superior temporal gyrus (STG) and inferior frontal gyrus (IFG) samples. RESULTS: Samples from 72 AD patients and 62 age-matched cognitively normal controls were assayed using Illumina© Infinium MethylationEPIC BeadChip. Five and 14 differentially methylated positions (DMPs) associated with pathology (i.e., Braak stage) with p value less than Bonferroni correction threshold of 6.79 × 10-8 in the STG and IFG were identified, respectively. These cytosine-phosphate-guanine (CpG) sites included promoter associated cg26263477 annotated to ABCA7 in the STG (p = 1.21 × 10-11), and cg14058329 annotated to the HOXA5/HOXA3/HOXA-AS3 gene cluster (p = 1.62 × 10-9) and cg09448088 (p = 3.95 × 10-9) annotated to MCF2L in the IFG. These genes were previously reported to harbor DMPs and/or differentially methylated regions (DMRs). Previously reported DMPs annotated to RMGA, GNG7, HOXA3, GPR56, SPG7, PCNT, RP11-961A15.1, MCF2L, RHBDF2, ANK1, PCNT, TPRG1, and RASGEF1C were replicated (p < 0.0001). One hundred twenty-one and 173 DMRs associated with pathology in the STG and IFG, respectively, were additionally identified. Of these, DMRs annotated to 30 unique genes were also identified as significant DMRs in the same brain region in a recent meta-analysis, while additional DMRs annotated to 12 genes were reported as DMRs in a different brain region or in a cross-cortex meta-analysis. The significant DMRs were enriched in promoters, CpG islands, and exons in the genome. Gene set enrichment analysis of DMPs and DMRs showed that gene sets involved in neuroinflammation (e.g., microglia differentiation), neurogenesis, and cognition were enriched (false discovery rate (FDR) < 0.05). CONCLUSIONS: Twenty-two DMPs and 30 DMRs associated with pathology were replicated, and novel DMPs and DMRs were discovered. SN - 1868-7083 UR - https://www.unboundmedicine.com/medline/citation/33069246/Epigenome_wide_association_study_of_Alzheimer's_disease_replicates_22_differentially_methylated_positions_and_30_differentially_methylated_regions_ DB - PRIME DP - Unbound Medicine ER -