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GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.
- Source :
- Journals of Gerontology Series A: Biological Sciences & Medical Sciences; Jan2015, Vol. 70 Issue 1, p110-118, 9p
- Publication Year :
- 2015
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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)).<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10795006
- Volume :
- 70
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journals of Gerontology Series A: Biological Sciences & Medical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 103864692
- Full Text :
- https://doi.org/10.1093/gerona/glu166