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Meta-Analysis
. 2015 Jan;70(1):110-8.
doi: 10.1093/gerona/glu166. Epub 2014 Sep 8.

GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy

Linda Broer  1 , Aron S Buchman  2 , Joris Deelen  3 , Daniel S Evans  4 , Jessica D Faul  5 , Kathryn L Lunetta  6 , Paola Sebastiani  7 , Jennifer A Smith  8 , Albert V Smith  9 , Toshiko Tanaka  10 , Lei Yu  2 , Alice M Arnold  11 , Thor Aspelund  9 , Emelia J Benjamin  12 , Philip L De Jager  13 , Gudny Eirkisdottir  14 , Denis A Evans  15 , Melissa E Garcia  16 , Albert Hofman  17 , Robert C Kaplan  18 , Sharon L R Kardia  8 , Douglas P Kiel  19 , Ben A Oostra  17 , Eric S Orwoll  20 , Neeta Parimi  4 , Bruce M Psaty  21 , Fernando Rivadeneira  22 , Jerome I Rotter  23 , Sudha Seshadri  24 , Andrew Singleton  25 , Henning Tiemeier  26 , André G Uitterlinden  1 , Wei Zhao  8 , Stefania Bandinelli  27 , David A Bennett  2 , Luigi Ferrucci  10 , Vilmundur Gudnason  9 , Tamara B Harris  16 , David Karasik  28 , Lenore J Launer  16 , Thomas T Perls  29 , P Eline Slagboom  3 , Gregory J Tranah  30 , David R Weir  5 , Anne B Newman  31 , Cornelia M van Duijn  32 , Joanne M Murabito  33
Affiliations
Meta-Analysis

GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy

Linda Broer et al. J Gerontol A Biol Sci Med Sci. 2015 Jan.

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.

Keywords: APOE.; FOXO3; GWAS; Longevity.

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References

    1. Bohni R, Riesgo-Escovar J, Oldham S, et al. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell. 1999;97:865–875. :S0092-8674(00)80799-0 [pii] - PubMed
    1. Clancy DJ, Gems D, Harshman LG, et al. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science. 2001;292:104–106. :10.1126/science.1057991 292/5514/104 [pii] - PubMed
    1. Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ. Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology. 2000;141:2608–2613. - PubMed
    1. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993;366:461–464. :10.1038/366461a0 - PubMed
    1. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans . Science (New York). 1997;277:942–946. - PubMed

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