TY - JOUR
T1 - APOE Alleles and extreme human longevity
AU - Sebastiani, Paola
AU - Gurinovich, Anastasia
AU - Nygaard, Marianne
AU - Sasaki, Takashi
AU - Sweigart, Benjamin
AU - Bae, Harold
AU - Andersen, Stacy L.
AU - Villa, Francesco
AU - Atzmon, Gil
AU - Christensen, Kaare
AU - Arai, Yasumichi
AU - Barzilai, Nir
AU - Puca, Annibale
AU - Christiansen, Lene
AU - Hirose, Nobuyoshi
AU - Perls, Thomas T.
N1 - Publisher Copyright:
© 2018 The Author(s). Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - We assembled a collection of 28,297 participants from seven studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity, and the Health and Retirement Studies to investigate the association between the APOE alleles ϵ 2 ϵ 3 and ϵ 4 and extreme human longevity and age at death. By using three different genetic models and two definitions of extreme longevity based on either a threshold model or age at death, we show that ϵ 4 is associated with a substantially decreased odds for extreme longevity, and increased risk for death that persists even beyond ages reached by less than 1% of the population. We also show that carrying the ϵ 2 ϵ 2 or ϵ 2 ϵ 3 genotype is associated with significantly increased odds to reach extreme longevity, with decreased risk for death compared with carrying the genotype ϵ 3 ϵ 3 but with only a modest reduction in risk for death beyond an age reached by less than 1% of the population.
AB - We assembled a collection of 28,297 participants from seven studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity, and the Health and Retirement Studies to investigate the association between the APOE alleles ϵ 2 ϵ 3 and ϵ 4 and extreme human longevity and age at death. By using three different genetic models and two definitions of extreme longevity based on either a threshold model or age at death, we show that ϵ 4 is associated with a substantially decreased odds for extreme longevity, and increased risk for death that persists even beyond ages reached by less than 1% of the population. We also show that carrying the ϵ 2 ϵ 2 or ϵ 2 ϵ 3 genotype is associated with significantly increased odds to reach extreme longevity, with decreased risk for death compared with carrying the genotype ϵ 3 ϵ 3 but with only a modest reduction in risk for death beyond an age reached by less than 1% of the population.
KW - APOE
KW - Extreme human longevity
KW - Genetic association
KW - Survival distribution
UR - http://www.scopus.com/inward/record.url?scp=85058571306&partnerID=8YFLogxK
U2 - 10.1093/gerona/gly174
DO - 10.1093/gerona/gly174
M3 - Article
C2 - 30060062
AN - SCOPUS:85058571306
SN - 1079-5006
VL - 74
SP - 44
EP - 51
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 1
ER -