ArticleHuman molecular genetics2020
DNA methylation QTL analysis identifies new regulators of human longevity.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Specific Marker Gene Analysis for Primary Central Nervous System Lymphoma Based on Methylation Difference and Development of Detection Primers.Brain and behavior · 2025Article
- The landscape of aging.Science China. Life sciences · 2022Review
- Long-Lived Individuals Show a Lower Burden of Variants Predisposing to Age-Related Diseases and a Higher Polygenic Longevity Score.International journal of molecular sciences · 2022Article
- Role of the mtDNA Mutations and Mitophagy in Inflammaging.International journal of molecular sciences · 2022Review
- GPCRs Are Optimal Regulators of Complex Biological Systems and Orchestrate the Interface between Health and Disease.International journal of molecular sciences · 2021Review
- Association ofCells · 2021Article
- Smart-RRBS for single-cell methylome and transcriptome analysis.Nature protocols · 2021Review
- Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Multi-Omics Approaches in Immunological Research.Frontiers in immunology · 2021Review
- Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis.Clinical epigenetics · 2020Article
- Quantitative comparison of within-sample heterogeneity scores for DNA methylation data.Nucleic acids research · 2020Article
- Impacts of Epigenetic Processes on the Health and Productivity of Livestock.Frontiers in genetics · 2020Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
Human longevity is a complex trait influenced by both genetic and environmental factors, whose interaction is mediated by epigenetic mechanisms like DNA methylation. Here, we generated genome-wide whole-blood methylome data from 267 individuals, of which 71 were long-lived (90-104 years), by applying reduced representation bisulfite sequencing. We followed a stringent two-stage analysis procedure using discovery and replication samples to detect differentially methylated sites (DMSs) between young and long-lived study participants. Additionally, we performed a DNA methylation quantitative trait loci analysis to identify DMSs that underlie the longevity phenotype. We combined the DMSs results with gene expression data as an indicator of functional relevance. This approach yielded 21 new candidate genes, the majority of which are involved in neurophysiological processes or cancer. Notably, two candidates (PVRL2, ERCC1) are located on chromosome 19q, in close proximity to the well-known longevity- and Alzheimer's disease-associated loci APOE and TOMM40. We propose this region as a longevity hub, operating on both a genetic (APOE, TOMM40) and an epigenetic (PVRL2, ERCC1) level. We hypothesize that the heritable methylation and associated gene expression changes reported here are overall advantageous for the LLI and may prevent/postpone age-related diseases and facilitate survival into very old age.
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Registered trials
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