Genome-wide DNA methylation profiling in nonagenarians suggests an effect of PM20D1 in late onset Alzheimer's disease

Carolina Coto-Vílchez, José J. Martínez-Magaña, Lara Mora-Villalobos, Daniel Valerio, Alma D. Genis-Mendoza, Jeremy M. Silverman, Humberto Nicolini, Henriette Raventós, Gabriela Chavarria-Soley

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background The aim of this study is to identify differentially methylated regions (DMRs) in the genomes of a sample of cognitively healthy individuals and a sample of individuals with LOAD, all of them nonagenarians from Costa Rica. Methods In this study, we compared whole blood DNA methylation profiles of 32 individuals: 21 cognitively healthy and 11 with LOAD, using the Infinium MethylationEPIC BeadChip. First, we calculated the epigenetic age of the participants based on Horvath's epigenetic clock. DMRcate and Bumphunter were used to identify DMRs. After in silico and knowledge-based filtering of the DMRs, we performed a methylation quantitative loci (mQTL) analysis (rs708727 and rs960603). Results On average, the epigenetic age was 73 years in both groups, which represents a difference of over 20 years between epigenetic and chronological age in both affected and unaffected individuals. Methylation analysis revealed 11 DMRs between groups, which contain six genes and two pseudogenes. These genes are involved in cell cycle regulation, embryogenesis, synthesis of ceramides, and migration of interneurons to the cerebral cortex. One of the six genes is PM20D1, for which altered expression has been reported in LOAD. After genotyping previously reported mQTL SNPs for the gene, we found that average methylation in the PM20D1 DMR differs between genotypes for rs708727, but not for rs960603. Conclusions This work supports the possible role of PM20D1 in protection against AD, by showing differential methylation in blood of affected and unaffected nonagenarians. Our results also support the influence of genetic factors on PM20D1 methylation levels.

Original languageEnglish
Pages (from-to)174-182
Number of pages9
JournalCNS Spectrums
Issue number2
StatePublished - 16 Apr 2023


  • Late-onset Alzheimer's disease
  • PM20D1
  • epigenome
  • quantitative-trait loci


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