title: Apolipoprotein E and familial longevity.
abstract: Exceptional longevity is associated with substantial heritability. The ε4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ε2 allele with decreased mortality, although inconsistently. Offspring from long-lived families and spouse controls were recruited at 3 sites in the United States and Denmark. We used generalized estimating equations to compare the likelihood of carrying risk alleles in offspring (n = 2307) and spouse controls (n = 764), adjusting for age, sex, level of education, and family membership. The likelihood of carrying an APOE ε4 allele or a G allele in rs2075650 was lower (odds ratio [OR], 0.75; p = 0.005 and OR, 0.70; p = 0.002) and the likelihood of carrying an APOE ε2 allele was higher (OR, 1.5; p = 0.007) among family members in the offspring generation than among their spouse controls. Our findings support the hypothesis that both reduction in the frequency of the ε4 allele and increase in the frequency of the ε2 allele contribute to longevity.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA. ns24@columbia.edu
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
authors.forename: Sandra
authors.initials: S
authors.lastname: Barral
authors.forename: Thomas
authors.initials: T
authors.lastname: Perls
authors.forename: Anne
authors.initials: A
authors.lastname: Newman
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.forename: Michael
authors.initials: M
authors.lastname: Province
authors.forename: Winifred K
authors.initials: WK
authors.lastname: Rossi
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D001053:Apolipoproteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016019:Survival Analysis; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
chemical_list: D001053:Apolipoproteins