title: No Association between Variation in Longevity Candidate Genes and Aging-related Phenotypes in Oldest-old Danes.
abstract: In this study we explored the association between aging-related phenotypes previously reported to predict survival in old age and variation in 77 genes from the DNA repair pathway, 32 genes from the growth hormone 1/ insulin-like growth factor 1/insulin (GH/IGF-1/INS) signalling pathway and 16 additional genes repeatedly considered as candidates for human longevity: APOE, APOA4, APOC3, ACE, CETP, HFE, IL6, IL6R, MTHFR, TGFB1, SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. Altogether, 1,049 single nucleotide polymorphisms (SNPs) were genotyped in 1,088 oldest-old (age 92-93 years) Danes and analysed with phenotype data on physical functioning (hand grip strength), cognitive functioning (mini mental state examination and a cognitive composite score), activity of daily living and self-rated health. Five SNPs showed association to one of the phenotypes; however, none of these SNPs were associated with a change in the relevant phenotype over time (7 years of follow-up) and none of the SNPs could be confirmed in a replication sample of 1,281 oldest-old Danes (age 94-100). Hence, our study does not support association between common variation in the investigated longevity candidate genes and aging-related phenotypes consistently shown to predict survival. It is possible that larger sample sizes are needed to robustly reveal associations with small effect sizes.
authors.affiliation: Epidemiology, Biostatistics and Biodemography, The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark; Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. Electronic address: msoerensen@health.sdu.dk.
authors.forename: Mette
authors.initials: M
authors.lastname: Soerensen
authors.affiliation: Epidemiology, Biostatistics and Biodemography, The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark; Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. Electronic address: mnygaard@health.sdu.dk.
authors.forename: Marianne
authors.initials: M
authors.lastname: Nygaard
authors.affiliation: Epidemiology, Biostatistics and Biodemography, The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark. Electronic address: bdebrabant@health.sdu.dk.
authors.forename: Birgit
authors.initials: B
authors.lastname: Debrabant
authors.affiliation: Epidemiology, Biostatistics and Biodemography, The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark; Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. Electronic address: jmengel-from@health.sdu.dk.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mengel-From
authors.affiliation: Department of Biology, Ecology and Earth Science, University of Calabria, Ponte Pietro Bucci cubo 4C, 87036 Rende (Cs), Italy. Electronic address: s.dato@unical.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Dato
authors.affiliation: Epidemiology, Biostatistics and Biodemography, The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark; Max-Planck Odense Center on the Biodemography of Aging, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark. Electronic address: mthinggaard@health.sdu.dk.
authors.forename: Mikael
authors.initials: M
authors.lastname: Thinggaard
authors.affiliation: Epidemiology, Biostatistics and Biodemography, The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark; Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark. Electronic address: kchristensen@health.sdu.dk.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Epidemiology, Biostatistics and Biodemography, The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark. Electronic address: lchristiansen@health.sdu.dk.
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
mesh_terms: D000203:Activities of Daily Living; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D003071:Cognition; D003718:Denmark; D005260:Female; D005838:Genotype; D018737:Hand Strength; D006801:Humans; D016014:Linear Models; D008136:Longevity / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics*; D011795:Surveys and Questionnaires
keywords: Association study; Human aging; Oldest-old; Single nucleotide polymorphisms