Bioinformatic and genomic analysis identifies C allele of APOE rs7412 as the most prominent variant limiting extreme human longevity

Sci Rep. 2025 Jul 1;15(1):21688. doi: 10.1038/s41598-025-02848-5.

Abstract

The genetic factors influencing human longevity have long been a subject of curiosity, linking ancient historical records with modern genomic research. This study seeks to identify key genetic contributors to lifespan by integrating genome-wide association studies (GWAS) with functional annotations across multiple biological databases. Among our findings, APOE emerged as one of the most prominent gene, with the rs7412-C variant showing a strong association with reduced lifespan due to its widely distributed across global populations. Additionally, we observed that rs449647-A and rs405509-T were more frequently found in regions with longer life expectancies, such as Asia, and were less common in African populations, suggesting a possible genetic influence on regional lifespan variations. These findings provide a basis for future research into the genetic mechanisms underlying aging and may contribute to the development of strategies to promote healthy aging.

Keywords: APOE; Bioinformatics; GWAS; Longevity; SNP.

MeSH terms

  • Alleles*
  • Apolipoproteins E* / genetics
  • Computational Biology* / methods
  • Genome-Wide Association Study
  • Genomics / methods
  • Humans
  • Longevity* / genetics
  • Polymorphism, Single Nucleotide*

Substances

  • Apolipoproteins E
  • ApoE protein, human