Meta‐analysis of genetic variants associated with human exceptional longevity.

Authors: Sebastiani P; Bae H; Sun FX; Andersen SL; Daw EW; Malovini A; Kojima T; Hirose N; Schupf N; Puca A; Perls TT

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.

Keywords: Aged, 80 and over; Aging/genetics; Alzheimer Disease/genetics; Case-Control Studies; Coronary Artery Disease/genetics; Female; Gene Regulatory Networks; Genetic Markers; *Genetic Variation; Genome-Wide Association Study; Humans; Longevity/*genetics; Male; Polymorphism, Single Nucleotide
Journal: Aging
Volume: 5
Issue: 9
Pages: 653-61
Date: Nov. 19, 2013
PMID: 24244950
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Sebastiani P, Bae H, Sun FX, Andersen SL, Daw EW, Malovini A, Kojima T, Hirose N, Schupf N, Puca A, Perls TT (2013) Meta‐analysis of genetic variants associated with human exceptional longevity. Aging 5: 653-61.

Longevity Variant Associations (p-value):
  • rs2075650 (4.44e-16)
  • rs1525501 (4.94e-06)
  • rs3803833 (2.72e-05)
  • rs1016013 (2.87e-05)
  • rs216148 (6.36e-05)
  • rs1867102 (7.28e-05)
  • rs1822590 (7.57e-05)
  • rs4918255 (8.81e-05)
  • rs1456669 (9.89e-05)
  • rs915179 (0.0001)
  • rs2738679 (6.85e-05)
  • rs17702471 (8.33e-05)
  • rs1042663 (8.39e-05)
  • rs651922 (0.00018)
  • rs11218921 (5.47e-05)
  • rs2738173 (0.00016)
  • rs1525501 (8.97e-05)
  • rs1456669 (0.000312)
  • rs4729049 (0.001311)
  • rs11954180 (0.001639)
  • rs2596230 (0.000383)
  • rs1800392 (0.000708)

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