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Research Paper|Volume 5, Issue 9|pp 653—661

Meta-analysis of genetic variants associated with human exceptional longevity

Paola Sebastiani1, Harold Bae, Fangui X. Sun1, Stacy L. Andersen2, E. Warwick Daw3, Alberto Malovini4, Toshio Kojima5, Nobuyoshi Hirose6, Nicole Schupf7, Annibale Puca8, Thomas T Perls2
  • 1Department of Biostatistics, Boston University School of Public Health, Boston MA 02118, USA
  • 2Section of Geriatrics, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA
  • 3Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO 63110, USA
  • 4Laboratorio di Informatica Biomedica, Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Pavia, Italy
  • 5Research Center for Physical Fitness, Sports and Health, Toyohashi University of Technology, Toyohashi, Japan
  • 6Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  • 7Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA
  • 8Unit of Genetics, Cardiovascular Research Institute Istituto Ricovero Cura Carattere Scientifico Multimedica, Sesto S. Giovanni, Italy; Facolta' di Medicina, Universita' di Salerno, Baronissi, Italy
Received: August 2, 2013Accepted: August 22, 2013Published: August 24, 2013
https://doi.org/10.18632/aging.100594

Copyright: © 2013 Sebastiani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Despite evidence from family studies that there is a strong genetic influence upon exceptional longevity, relatively few genetic variants have been associated with this trait. One reason could be that many genes individually have such weak effects that they cannot meet standard thresholds of genome wide significance, but as a group in specific combinations of genetic variations, they can have a strong influence. Previously we reported that such genetic signatures of 281 genetic markers associated with about 130 genes can do a relatively good job of differentiating centenarians from non-centenarians particularly if the centenarians are 106 years and older. This would support our hypothesis that the genetic influence upon exceptional longevity increases with older and older (and rarer) ages. We investigated this list of markers using similar genetic data from 5 studies of centenarians from the USA, Europe and Japan. The results from the meta-analysis show that many of these variants are associated with survival to these extreme ages in other studies. Since many centenarians compress morbidity and disability towards the end of their lives, these results could point to biological pathways and therefore new therapeutics to increase years of healthy lives in the general population.