A genome-wide association study of aging

Stefan Walter, Gil Atzmon, Ellen W. Demerath, Melissa E. Garcia, Robert C. Kaplan, Meena Kumari, Kathryn L. Lunetta, Yuri Milaneschi, Toshiko Tanaka, Gregory J. Tranah, Uwe Völker, Lei Yu, Alice Arnold, Emelia J. Benjamin, Reiner Biffar, Aron S. Buchman, Eric Boerwinkle, David Couper, Philip L. De Jager, Denis A. EvansTamara B. Harris, Wolfgang Hoffmann, Albert Hofman, David Karasik, Douglas P. Kiel, Thomas Kocher, Maris Kuningas, Lenore J. Launer, Kurt K. Lohman, Pamela L. Lutsey, Johan Mackenbach, Kristin Marciante, Bruce M. Psaty, Eric M. Reiman, Jerome I. Rotter, Sudha Seshadri, Michelle D. Shardell, Albert V. Smith, Cornelia van Duijn, Jeremy Walston, M. Carola Zillikens, Stefania Bandinelli, Sebastian E. Baumeister, David A. Bennett, Luigi Ferrucci, Vilmundur Gudnason, Mika Kivimaki, Yongmei Liu, Joanne M. Murabito, Anne B. Newman, Henning Tiemeier, Nora Franceschini

Research output: Contribution to journalArticle

96 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2109.e15-2109.e28
JournalNeurobiology of Aging
Volume32
Issue number11
DOIs
StatePublished - Nov 2011

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Keywords

  • Aging
  • Brain aging
  • Disease-free survival
  • Genome-wide association analysis
  • Longevity
  • Mortality

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Walter, S., Atzmon, G., Demerath, E. W., Garcia, M. E., Kaplan, R. C., Kumari, M., Lunetta, K. L., Milaneschi, Y., Tanaka, T., Tranah, G. J., Völker, U., Yu, L., Arnold, A., Benjamin, E. J., Biffar, R., Buchman, A. S., Boerwinkle, E., Couper, D., De Jager, P. L., ... Franceschini, N. (2011). A genome-wide association study of aging. Neurobiology of Aging, 32(11), 2109.e15-2109.e28. https://doi.org/10.1016/j.neurobiolaging.2011.05.026