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The FoxO3 gene and cause-specific mortality.

Publication ,  Journal Article
Willcox, BJ; Tranah, GJ; Chen, R; Morris, BJ; Masaki, KH; He, Q; Willcox, DC; Allsopp, RC; Moisyadi, S; Poon, LW; Rodriguez, B; Newman, AB ...
Published in: Aging Cell
August 2016

The G allele of the FOXO3 single nucleotide polymorphism (SNP) rs2802292 exhibits a consistently replicated genetic association with longevity in multiple populations worldwide. The aims of this study were to quantify the mortality risk for the longevity-associated genotype and to discover the particular cause(s) of death associated with this allele in older Americans of diverse ancestry. It involved a 17-year prospective cohort study of 3584 older American men of Japanese ancestry from the Honolulu Heart Program cohort, followed by a 17-year prospective replication study of 1595 white and 1056 black elderly individuals from the Health Aging and Body Composition cohort. The relation between FOXO3 genotype and cause-specific mortality was ascertained for major causes of death including coronary heart disease (CHD), cancer, and stroke. Age-adjusted and multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) for all-cause and cause-specific mortality. We found G allele carriers had a combined (Japanese, white, and black populations) risk reduction of 10% for total (all-cause) mortality (HR = 0.90; 95% CI, 0.84-0.95; P = 0.001). This effect size was consistent across populations and mostly contributed by 26% lower risk for CHD death (HR = 0.74; 95% CI, 0.64-0.86; P = 0.00004). No other causes of death made a significant contribution to the survival advantage for G allele carriers. In conclusion, at older age, there is a large risk reduction in mortality for G allele carriers, mostly due to lower CHD mortality. The findings support further research on FOXO3 and FoxO3 protein as potential targets for therapeutic intervention in aging-related diseases, particularly cardiovascular disease.

Duke Scholars

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Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

August 2016

Volume

15

Issue

4

Start / End Page

617 / 624

Location

England

Related Subject Headings

  • White People
  • Tumor Necrosis Factor-alpha
  • Risk Factors
  • Multivariate Analysis
  • Mortality
  • Male
  • Humans
  • Heterozygote
  • Genetic Predisposition to Disease
  • Forkhead Box Protein O3
 

Citation

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ICMJE
MLA
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Willcox, B. J., Tranah, G. J., Chen, R., Morris, B. J., Masaki, K. H., He, Q., … Donlon, T. A. (2016). The FoxO3 gene and cause-specific mortality. Aging Cell, 15(4), 617–624. https://doi.org/10.1111/acel.12452
Willcox, Bradley J., Gregory J. Tranah, Randi Chen, Brian J. Morris, Kamal H. Masaki, Qimei He, D Craig Willcox, et al. “The FoxO3 gene and cause-specific mortality.Aging Cell 15, no. 4 (August 2016): 617–24. https://doi.org/10.1111/acel.12452.
Willcox BJ, Tranah GJ, Chen R, Morris BJ, Masaki KH, He Q, et al. The FoxO3 gene and cause-specific mortality. Aging Cell. 2016 Aug;15(4):617–24.
Willcox, Bradley J., et al. “The FoxO3 gene and cause-specific mortality.Aging Cell, vol. 15, no. 4, Aug. 2016, pp. 617–24. Pubmed, doi:10.1111/acel.12452.
Willcox BJ, Tranah GJ, Chen R, Morris BJ, Masaki KH, He Q, Willcox DC, Allsopp RC, Moisyadi S, Poon LW, Rodriguez B, Newman AB, Harris TB, Cummings SR, Liu Y, Parimi N, Evans DS, Davy P, Gerschenson M, Donlon TA. The FoxO3 gene and cause-specific mortality. Aging Cell. 2016 Aug;15(4):617–624.
Journal cover image

Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

August 2016

Volume

15

Issue

4

Start / End Page

617 / 624

Location

England

Related Subject Headings

  • White People
  • Tumor Necrosis Factor-alpha
  • Risk Factors
  • Multivariate Analysis
  • Mortality
  • Male
  • Humans
  • Heterozygote
  • Genetic Predisposition to Disease
  • Forkhead Box Protein O3