Genetic Signatures of Exceptional Longevity in Humans

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Science  01 Jul 2010:
DOI: 10.1126/science.1190532

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Healthy aging is thought to reflect the combined influence of environmental factors (lifestyle choices) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity (EL) in 1055 centenarians and 1267 controls. Using these data, we built a genetic classification model that is based on 150 single-nucleotide polymorphisms (SNPs). When we applied this model to an independent set of centenarians and control individuals of average longevity (AL), we found that it correctly classified individuals into the EL or AL group 77% of the time. Further in silico analysis revealed that 90% of centenarians can be grouped into 19 clusters characterized by different combinations of SNP genotypes—or genetic signatures—of varying predictive value. The different signatures, which attest to the genetic complexity of EL, correlated with differences in the prevalence and age of onset of age-associated diseases (e.g., dementia, hypertension, and cardiovascular disease) and may help dissect this complex phenotype into subphenotypes of healthy aging.