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Aged
Aged, 80 and over
Apolipoproteins E/*genetics
Cell Adhesion Molecules/genetics
Cohort Studies
Female
Forkhead Box Protein O3
Forkhead Transcription Factors/*genetics
Genome-Wide Association Study
Humans
Longevity/*genetics
Male
Middle Aged
Polymorphism, Single Nucleotide
Receptors, Kainic Acid/genetics
Apoe.
Foxo3
Gwas
Longevity
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 x 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 x 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 = 1.85x10(-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.
