title: Genetic landscape of APOE in human longevity revealed by high-throughput sequencing.
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 2kb 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.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Seungjin
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Atzmon
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.affiliation: Division of Geriatrics and Clinical Gerontology, National Institute on Aging, Bethesda, MD 20892, USA.
authors.forename: Nalini
authors.initials: N
authors.lastname: Raghavachari
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: yousin.suh@einstein.yu.edu.
authors.forename: Yousin
authors.initials: Y
authors.lastname: Suh
mesh_terms: D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007585:Jews; D008136:Longevity / Q000235:genetics*; D008297:Male; D016366:Open Reading Frames / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E
keywords: APOE; Centenarian; Genetic variant; Longevity; Pooled target capture sequencing