Genetic landscape of APOE in human longevity revealed by high-throughput sequencing

Seungjin Ryu, Gil Atzmon, Nir Barzilai, Nalini Raghavachari, Yousin Suh

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Apolipoprotein E (APOE) gene has been the most replicated longevity-associated gene in humans. Two common APOE alleles are either significantly depleted (ε4 allele) or enriched (ε2 allele) in long-lived individuals as compared to controls. We performed high-throughput sequencing analysis of exons and 2 kb proximal promoter of APOE in 450 centenarians and 500 controls of Ashkenazi Jewish decent. We found two common regulatory variants, rs405509 (p = 0.006) and rs769449 (p = 0.036), that were significantly depleted in centenarians. Genotyping analysis of rs7412 and rs429358 showed significant enrichment of ε2 allele (p = 0.003) and ε2/ε3 genotype (p = 0.005), and significant depletion of ε3/ε4 genotype (p = 0.005) in centenarians. Our findings support the hypothesis that variants in both coding and regulatory regions of APOE may contribute to longevity in humans.

Original languageEnglish (US)
Pages (from-to)7-9
Number of pages3
JournalMechanisms of Ageing and Development
Volume155
DOIs
StatePublished - Apr 1 2016

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Keywords

  • APOE
  • Centenarian
  • Genetic variant
  • Longevity
  • Pooled target capture sequencing

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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