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

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

doi:10.1016/j.mad.2016.02.010

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 journal › Article › peer-review

29 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 language	English (US)
Pages (from-to)	7-9
Number of pages	3
Journal	Mechanisms of Ageing and Development
Volume	155
DOIs	https://doi.org/10.1016/j.mad.2016.02.010
State	Published - Apr 1 2016

Keywords

APOE
Centenarian
Genetic variant
Longevity
Pooled target capture sequencing

ASJC Scopus subject areas

Aging
Developmental Biology

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10.1016/j.mad.2016.02.010

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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 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.",

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author = "Seungjin Ryu and Gil Atzmon and Nir Barzilai and Nalini Raghavachari and Yousin Suh",

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AU - Ryu, Seungjin

AU - Atzmon, Gil

AU - Barzilai, Nir

AU - Raghavachari, Nalini

AU - Suh, Yousin

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - APOE

KW - Centenarian

KW - Genetic variant

KW - Longevity

KW - Pooled target capture sequencing

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

Abstract

Keywords

ASJC Scopus subject areas

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