Title | A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Levine, ME, Crimmins, EM |
Journal | J Gerontol A Biol Sci Med Sci |
Volume | 71 |
Issue | 6 |
Pagination | 703-12 |
Date Published | 2016 06 |
ISSN Number | 1758-535X |
Keywords | Aged, Aged, 80 and over, Aging, Alleles, Case-Control Studies, Gene Regulatory Networks, Genome-Wide Association Study, Genotype, Humans, Longevity, Longitudinal Studies, Middle Aged, Neoplasms, Phenotype, Polymorphism, Single Nucleotide, Smoking, Stress, Physiological, United States |
Abstract | Human longevity and diseases are likely influenced by multiple interacting genes within a few biologically conserved pathways. Using long-lived smokers as a phenotype (n = 90)-a group whose survival may signify innate resilience-we conducted a genome-wide association study comparing them to smokers at ages 52-69 (n = 730). These results were used to conduct a functional interaction network and pathway analysis, to identify single nucleotide polymorphisms that collectively related to smokers' longevity. We identified a set of 215 single nucleotide polymorphisms (all of which had p <5×10(-3) in the genome-wide association study) that were located within genes making-up a functional interaction network. These single nucleotide polymorphisms were then used to create a weighted polygenic risk score that, using an independent validation sample of nonsmokers (N = 6,447), was found to be significantly associated with a 22% increase in the likelihood of being aged 90-99 (n = 253) and an over threefold increase in the likelihood of being a centenarian (n = 4), compared with being at ages 52-79 (n = 4,900). Additionally, the polygenic risk score was also associated with an 11% reduction in cancer prevalence over up to 18 years (odds ratio: 0.89, p = .011). Overall, using a unique phenotype and incorporating prior knowledge of biological networks, this study identified a set of single nucleotide polymorphisms that together appear to be important for human aging, stress resistance, cancer, and longevity. |
DOI | 10.1093/gerona/glv141 |
User Guide Notes | |
Alternate Journal | J. Gerontol. A Biol. Sci. Med. Sci. |
Citation Key | 8662 |
PubMed ID | 26355015 |
PubMed Central ID | PMC4888382 |
Grant List | P30 AG017265 / AG / NIA NIH HHS / United States T32 AG000037 / AG / NIA NIH HHS / United States U01 AG009740 / AG / NIA NIH HHS / United States |