{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:40:54Z","timestamp":1790761254298,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T00:00:00Z","timestamp":1417478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003035","name":"Aase og Ejnar Danielsens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 AG08761"],"award-info":[{"award-number":["P01 AG08761"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u00e2\u20ac\u2122s Seventh Framework Programme (FP7\/2007-2011)","award":["259679"],"award-info":[{"award-number":["259679"]}]},{"name":"Max-Planck Institute for Demographic Research (Rostock, Germany)"},{"name":"The Br\u00c3\u00b8drene Hartmann Foundation"},{"name":"The Danish Council for Independent Research \u00e2\u20ac\u201c Medical Sciences"},{"name":"The Einer Willumsens Mindelegat Foundation"},{"name":"The INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N. (the European Regional Development Fund)"},{"name":"The King Christian the 10th foundation"},{"name":"The Novo Nordisk Foundation"},{"name":"The Velux Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic>FOXO3A<\/jats:italic> variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether <jats:italic>FOXO3A<\/jats:italic> variation also associates with aging\u2010related traits. Here, we investigate the association of 15 <jats:italic>FOXO3A<\/jats:italic> tagging single nucleotide polymorphisms (SNPs) in 1088 oldest\u2010old Danes (age 92\u201393) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self\u2010rated health. Based on previous studies in humans and foxo animal models, we also explore self\u2010reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur\/spine\/hip\/wrist) fracture. Gene\u2010based testing revealed significant associations of <jats:italic>FOXO3A<\/jats:italic> variation with ADL (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.044) and bone fracture (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.006). The single\u2010SNP statistics behind the gene\u2010based 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 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.054), while ADL did not (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.396). Although the single\u2010SNP associations did not formally replicate in another study population of oldest\u2010old Danes (<jats:italic>n<\/jats:italic>\u00a0=\u00a01279, age 94\u2013100), 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 <jats:italic>P<\/jats:italic>\u2010values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.<\/jats:p>","DOI":"10.1111\/acel.12295","type":"journal-article","created":{"date-parts":[[2014,12,3]],"date-time":"2014-12-03T08:43:06Z","timestamp":1417596186000},"page":"60-66","source":"Crossref","is-referenced-by-count":47,"title":["Association study of <i>FOXO3A<\/i> SNPs and aging phenotypes in Danish oldest\u2010old individuals"],"prefix":"10.1111","volume":"14","author":[{"given":"Mette","family":"Soerensen","sequence":"first","affiliation":[{"name":"The Danish Aging Research Center, Epidemiology Biostatistics and Biodemography Institute of Public Health University of Southern Denmark J.B. Winsloews Vej 9B 5000 Odense C Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital Sdr. Boulevard 29 5000 Odense C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Nygaard","sequence":"additional","affiliation":[{"name":"The Danish Aging Research Center, Epidemiology Biostatistics and Biodemography Institute of Public Health University of Southern Denmark J.B. Winsloews Vej 9B 5000 Odense C Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital Sdr. Boulevard 29 5000 Odense C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Dato","sequence":"additional","affiliation":[{"name":"The Danish Aging Research Center, Epidemiology Biostatistics and Biodemography Institute of Public Health University of Southern Denmark J.B. Winsloews Vej 9B 5000 Odense C Denmark"},{"name":"Department of Biology, Ecology and Earth Science University of Calabria Ponte Pietro Bucci cubo 4C 87036 Rende (Cs) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinna","family":"Stevnsner","sequence":"additional","affiliation":[{"name":"The Danish Aging Research Center Department of Molecular Biology and Genetics Aarhus University C. F. Moellers All\u00e9 3 8000 Aarhus C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilhelm A.","family":"Bohr","sequence":"additional","affiliation":[{"name":"The Danish Aging Research Center Department of Molecular Biology and Genetics Aarhus University C. F. Moellers All\u00e9 3 8000 Aarhus C Denmark"},{"name":"Laboratory of Molecular Gerontology National Institute on Aging National Institute of Health 251 Bayview Boulevard 21224\u20106825 Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaare","family":"Christensen","sequence":"additional","affiliation":[{"name":"The Danish Aging Research Center, Epidemiology Biostatistics and Biodemography Institute of Public Health University of Southern Denmark J.B. Winsloews Vej 9B 5000 Odense C Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital Sdr. Boulevard 29 5000 Odense C Denmark"},{"name":"Department of Biochemistry and Pharmacology Odense University Hospital Sdr. Boulevard 29 5000 Odense C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene","family":"Christiansen","sequence":"additional","affiliation":[{"name":"The Danish Aging Research Center, Epidemiology Biostatistics and Biodemography Institute of Public Health University of Southern Denmark J.B. Winsloews Vej 9B 5000 Odense C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.12.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2008.0827"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.27"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0881"},{"issue":"5","key":"e_1_2_9_7_1","first-page":"769","article-title":"Association between FOXO3A gene polymorphisms and human longevity: a meta\u2010analysis","volume":"16","author":"Bao JM","year":"2014","journal-title":"Asian J Androl."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-003-1584-z"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/515197"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu166"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086336"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1871"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60777-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570161111666131218152807"},{"key":"e_1_2_9_16_1","first-page":"700","article-title":"Assessment and treatment of osteoporotic hip fractures (paper in Danish)","volume":"172","author":"Eiken PA","year":"2010","journal-title":"Ugeskr. 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