Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis

A genome-wide association study of aging

Stefan Walter et al. Neurobiol Aging. 2011 Nov.

Abstract

Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.

PubMed Disclaimer

Conflict of interest statement

Disclosure Statement

The authors declare that no competing interests exist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Figures

Figure 1
Figure 1
Figure 1a Quantile–quantile (Q-Q) plot after meta-analysis for time to death Figure 1b Quantile–quantile (Q-Q) plot after meta-analysis for time to event
Figure 1
Figure 1
Figure 1a Quantile–quantile (Q-Q) plot after meta-analysis for time to death Figure 1b Quantile–quantile (Q-Q) plot after meta-analysis for time to event
Figure 2
Figure 2. Network describing neuronal activities related to time to death
Pathway analysis of genes (SNPs) associated with time to death. Genes are represented as nodes; edges indicate known interactions (solid lines depict direct and hatched lines depict indirect interaction). Human gene functions are color-coded as follows: Red= Unknown, Yellow= Transmembrane Receptor and G-Protein Coupled Receptor, Magenta (Pink-Purple)= Group/Complex/Other, Bright Green= Ion Channel, Hunter Green (Dark Green) = Peptidase, Navy Blue = transcription regulator, Light Blue=Transporter, Beige= Enzyme, Orange= Kinase, Light green= Cytokine, Light Purple= Phosphate, Gray= Translation Regulator, Olive Green=Ligand-dependent nuclear receptor.
See this image and copyright information in PMC

References

    1. Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Martin J, Hebert S, Doelle H, Ersoy B, Kryukov G, Schmidt S, Yosef N, Ruppin E, Sharan R, Vaisse C, Sunyaev S, Dent R, Cohen J, McPherson R, Pennacchio LA. Medical sequencing at the extremes of human body mass. Am J Hum Genet. 2007;80(4):779–91. - PMC - PubMed
    1. Anselmi CV, Malovini A, Roncarati R, Novelli V, Villa F, Condorelli G, Bellazzi R, Puca AA. Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res. 2009;12(2):95–104. - PubMed
    1. Atzmon G, Schechter C, Greiner W, Davidson D, Rennert G, Barzilai N. Clinical phenotype of families with longevity. J Am Geriatr Soc. 2004;52(2):274–7. 52068 [pii] - PubMed
    1. Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature. 2010;464(7288):529–35. doi: 10.1038/nature08983. nature08983 [pii] - DOI - PMC - PubMed
    1. Blanpied TA, Scott DB, Ehlers MD. Age-related regulation of dendritic endocytosis associated with altered clathrin dynamics. Neurobiol Aging. 2003;24(8):1095–104. S0197458003001751 [pii] - PubMed

Publication types

Grants and funding