TY - JOUR
T1 - No Association between Variation in Longevity Candidate Genes and Aging-related Phenotypes in Oldest-old Danes
AU - Sørensen, Mette
AU - Nygaard, Marianne
AU - Debrabant, Birgit
AU - Mengel-From, Jonas
AU - Dato, Serena
AU - Thinggaard, Mikael
AU - Christensen, Kaare
AU - Christiansen, Lene
N1 - Copyright © 2016 Elsevier Inc. All rights reserved.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Association study
KW - Human aging
KW - Oldest-Old
KW - Single nucleotide polymorphisms
KW - Association study
KW - Human aging
KW - Oldest-old
KW - Single nucleotide polymorphisms
U2 - 10.1016/j.exger.2016.03.001
DO - 10.1016/j.exger.2016.03.001
M3 - Journal article
C2 - 26946122
VL - 78
SP - 57
EP - 61
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
ER -