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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.

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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.


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.


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)).


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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