Association study of FOXO3A SNPs and aging phenotypes in Danish oldest‐old individuals. Issue 1 (2nd December 2014)

• Record Type: Journal Article
• Authors: Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A.; Christensen, Kaare; Christiansen, Lene
• Is Part Of: Aging cell. Volume 14:Issue 1(2015:Feb.)
• Page Start: 60
• Page End: 66
• Publication Date: 2014-12-02
• Subjects: Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12295
• Languages: English
• ISSNs: 1474-9718

Abstract

<abstract abstract-type="main" id="acel12295-abs-0001"> <title>Summary</title> <p> <italic>FOXO3A</italic> variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether <italic>FOXO3A</italic> variation also associates with aging‐related traits. Here, we investigate the association of 15 <italic>FOXO3A</italic> 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 <italic>FOXO3A</italic> variation with ADL (<italic>P</italic> = 0.044) and bone fracture (<italic>P</italic> = 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 (<italic>P</italic> = 0.054), while ADL did not (<italic>P</italic> = 0.396). Although the single‐SNP associations did not formally replicate in another study population of oldest‐old Danes (<italic>n</italic> = 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 <italic>P</italic>‐values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.</p> </abstract>