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Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals

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  • Mette Soerensen, University of Southern Denmark, Denmark
  • Marianne Nygaard, University of Southern Denmark, Denmark
  • Serena Dato, University of Southern Denmark, Denmark
  • Tinna Stevnsner
  • Vilhelm Bohr, Laboratory of Molecular Gerontology, National Institute on Aging, National Institute of Health, 251 Bayview Boulevard, Baltimore, Unknown
  • Kaare Christensen, Department of Clinical Genetics, Odense University Hospital, Odense, Denmark., Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark., Denmark
  • Lene Christiansen, University of Southern Denmark, Denmark

FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.

Original languageEnglish
JournalAging Cell
Pages (from-to)60-66
Number of pages7
Publication statusPublished - Feb 2015

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