期刊
AGING CELL
卷 9, 期 6, 页码 1010-1017出版社
WILEY
DOI: 10.1111/j.1474-9726.2010.00627.x
关键词
human longevity; Forkhead box O3A (FOXO3A); association study; case-control and longitudinal data
资金
- Max-Planck Institute for Demographic Research, (Rostock, Germany)
- National Institute on Aging [P01 AG08761]
- European Regional Development Fund
- Novo Nordisk Foundation
- Aase and Ejnar Danielsen Foundation
- Augustinus Foundation
- Brodrene Hartmann Foundation
- King Christian the 10th foundation
- Einer Willumsens Mindelegat Foundation
- VELUX Foundation
Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case-control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the Danish 1905 cohort, N = 1089) and middle-aged Danes (N = 736), applying a longitudinal study design as well as the case-control study design. Fifteen SNPs were chosen in order to cover the known common variation in FOXO3A. Comparing SNP frequencies in the oldest old with middle-aged individuals, we found association (after correction for multiple testing) of eight SNPs; 4 (rs13217795, rs2764264, rs479744, and rs9400239) previously reported to be associated with longevity and four novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P-values 0.001-0.044). Moreover, we found association of the haplotypes TAC and CAC of rs9486902, rs10499051, and rs12206094 (corrected P-values: 0.01-0.03) with longevity. Finally, we here present data applying a longitudinal study design; when using follow-up survival data on the oldest old in a longitudinal analysis, we found no SNPs to remain significant after the correction for multiple testing (Bonferroni correction). Hence, our results support and extent the proposed role of FOXO3A as a candidate longevity gene for survival from younger ages to old age, yet not during old age.
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