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Genomics of human health and aging.

Publication ,  Journal Article
Kulminski, AM; Culminskaya, I
Published in: Age (Dordrecht, Netherlands)
April 2013

Despite notable progress of the candidate-gene and genome-wide association studies (GWAS), understanding the role of genes contributing to human health and lifespan is still very limited. We use the Framingham Heart Study to elucidate if recognizing the role of evolution and systemic processes in an aging organism could advance such studies. We combine throughput methods of GWAS with more detail methods typical for candidate-gene analyses and show that both lifespan and ages at onset of CVD and cancer can be controlled by the same allelic variants. The risk allele carriers are at highly significant risk of premature death (e.g., RR=2.9, p=5.0 × 10(-66)), onset of CVD (e.g., RR=1.6, p=4.6 × 10(-17)), and onset of cancer (e.g., RR=1.6, p=1.5 × 10(-6)). The mechanism mediating the revealed genetic associations is likely associated with biological aging. These aging-related phenotypes are associated with a complex network which includes, in this study, 62 correlated SNPs even so these SNPs can be on non-homologous chromosomes. A striking result is three-fold, highly significant (p=3.6 × 10(-10)) enrichment of non-synonymous SNPs (N=27) in this network compared to the entire qualified set of the studied SNPs. Functional significance of this network is strengthened by involvement of genes for these SNPs in fundamental biological processes related to aging (e.g., response to stimuli, protein degradation, apoptosis) and by connections of these genes with neurological (20 genes) and cardio-vascular (nine genes) processes and tumorigenesis (10 genes). These results document challenging role of gene networks in regulating human health and aging and call for broadening focus on genomics of such phenotypes.

Duke Scholars

Published In

Age (Dordrecht, Netherlands)

DOI

EISSN

1574-4647

ISSN

0161-9152

Publication Date

April 2013

Volume

35

Issue

2

Start / End Page

455 / 469

Related Subject Headings

  • Proportional Hazards Models
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Nervous System Diseases
  • Neoplasms
  • Middle Aged
  • Linkage Disequilibrium
  • Humans
  • Gerontology
  • Genomics
 

Citation

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ICMJE
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Kulminski, A. M., & Culminskaya, I. (2013). Genomics of human health and aging. Age (Dordrecht, Netherlands), 35(2), 455–469. https://doi.org/10.1007/s11357-011-9362-x
Kulminski, Alexander M., and Irina Culminskaya. “Genomics of human health and aging.Age (Dordrecht, Netherlands) 35, no. 2 (April 2013): 455–69. https://doi.org/10.1007/s11357-011-9362-x.
Kulminski AM, Culminskaya I. Genomics of human health and aging. Age (Dordrecht, Netherlands). 2013 Apr;35(2):455–69.
Kulminski, Alexander M., and Irina Culminskaya. “Genomics of human health and aging.Age (Dordrecht, Netherlands), vol. 35, no. 2, Apr. 2013, pp. 455–69. Epmc, doi:10.1007/s11357-011-9362-x.
Kulminski AM, Culminskaya I. Genomics of human health and aging. Age (Dordrecht, Netherlands). 2013 Apr;35(2):455–469.
Journal cover image

Published In

Age (Dordrecht, Netherlands)

DOI

EISSN

1574-4647

ISSN

0161-9152

Publication Date

April 2013

Volume

35

Issue

2

Start / End Page

455 / 469

Related Subject Headings

  • Proportional Hazards Models
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Nervous System Diseases
  • Neoplasms
  • Middle Aged
  • Linkage Disequilibrium
  • Humans
  • Gerontology
  • Genomics