title: AKT1 fails to replicate as a longevity-associated gene in Danish and German nonagenarians and centenarians.
abstract: In addition to APOE and FOXO3, AKT1 has recently been suggested as a third consistent longevity gene, with variants in AKT1 found to be associated with human lifespan in two previous studies. Here, we evaluated AKT1 as a longevity-associated gene across populations by attempting to replicate the previously identified variant rs3803304 as well as by analyzing six additional AKT1 single-nucleotide polymorphisms, thus capturing more of the common variation in the gene. The study population was 2996 long-lived individuals (nonagenarians and centenarians) and 1840 younger controls of Danish and German ancestry. None of the seven SNPs tested were significantly associated with longevity in either a case-control or a longitudinal setting, although a supportive nominal indication of a disadvantageous effect of rs3803304 was found in a restricted group of Danish centenarian men. Overall, our results do not support AKT1 as a universal longevity-associated gene.
authors.affiliation: Epidemiology, Institute of Public Health, University of Southern Denmark, Odense C, Denmark. mnygaard@health.sdu.dk
authors.forename: Marianne
authors.initials: M
authors.lastname: Nygaard
authors.forename: Mette
authors.initials: M
authors.lastname: Soerensen
authors.forename: Friederike
authors.initials: F
authors.lastname: Flachsbart
authors.forename: Jonas
authors.initials: J
authors.lastname: Mengel-From
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Almut
authors.initials: A
authors.lastname: Nebel
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
mesh_terms: D000369:Aged, 80 and over; D003718:Denmark; D005260:Female; D005838:Genotype; D005858:Germany; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
chemical_list: C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt