Genetic Correlates of Longevity and Selected Age-Related Phenotypes: A Genome-Wide Association Study in the Framingham Study


Show simple item record Lunetta, Kathryn L en_US D'Agostino, Ralph B en_US Karasik, David en_US Benjamin, Emelia J en_US Guo, Chao-Yu en_US Govindaraju, Raju en_US Kiel, Douglas P en_US Kelly-Hayes, Margaret en_US Massaro, Joseph M en_US Pencina, Michael J en_US Seshadri, Sudha en_US Murabito, Joanne M en_US 2011-12-29T21:02:17Z 2011-12-29T21:02:17Z 2007 en_US 2007-9-19 en_US
dc.identifier.citation Lunetta, Kathryn L, Ralph B D'Agostino, David Karasik, Emelia J Benjamin, Chao-Yu Guo, Raju Govindaraju, Douglas P Kiel, Margaret Kelly-Hayes, Joseph M Massaro, Michael J Pencina, Sudha Seshadri, Joanne M Murabito. "Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study." BMC Medical Genetics 8 (Suppl 1):S13. (2007) en_US
dc.identifier.issn 1471-2350 en_US
dc.description.abstract BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS: We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate ≥80%, minor allele frequency ≥10%, Hardy-Weinberg test p ≥ 0.001). RESULTS: In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at . CONCLUSION. Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging. en_US
dc.description.sponsorship National Heart, Lung, and Blood Institute Framingham Heart Study (N01-HC-25195, R01 AR/AG 41398, AG028321); National Health Institutes National Center for Research Resources Shared Instrumentation Grant (ISI0R163736-01A1) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2007 Lunetta et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri en_US
dc.title Genetic Correlates of Longevity and Selected Age-Related Phenotypes: A Genome-Wide Association Study in the Framingham Study en_US
dc.type article en_US
dc.identifier.doi 10.1186/1471-2350-8-S1-S13 en_US
dc.identifier.pubmedid 17903295 en_US
dc.identifier.pmcid 1995604 en_US

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