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GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.

  • Author(s): Broer, Linda
  • Buchman, Aron S
  • Deelen, Joris
  • Evans, Daniel S
  • Faul, Jessica D
  • Lunetta, Kathryn L
  • Sebastiani, Paola
  • Smith, Jennifer A
  • Smith, Albert V
  • Tanaka, Toshiko
  • Yu, Lei
  • Arnold, Alice M
  • Aspelund, Thor
  • Benjamin, Emelia J
  • De Jager, Philip L
  • Eirkisdottir, Gudny
  • Evans, Denis A
  • Garcia, Melissa E
  • Hofman, Albert
  • Kaplan, Robert C
  • Kardia, Sharon LR
  • Kiel, Douglas P
  • Oostra, Ben A
  • Orwoll, Eric S
  • Parimi, Neeta
  • Psaty, Bruce M
  • Rivadeneira, Fernando
  • Rotter, Jerome I
  • Seshadri, Sudha
  • Singleton, Andrew
  • Tiemeier, Henning
  • Uitterlinden, André G
  • Zhao, Wei
  • Bandinelli, Stefania
  • Bennett, David A
  • Ferrucci, Luigi
  • Gudnason, Vilmundur
  • Harris, Tamara B
  • Karasik, David
  • Launer, Lenore J
  • Perls, Thomas T
  • Slagboom, P Eline
  • Tranah, Gregory J
  • Weir, David R
  • Newman, Anne B
  • van Duijn, Cornelia M
  • Murabito, Joanne M
  • et al.

Published Web Location

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296168/
No data is associated with this publication.
Abstract

BACKGROUND:The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies. METHODS:We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity. RESULTS:In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)). CONCLUSIONS:We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

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