Genetic signatures of exceptional longevity in humans.
Genetic signatures of exceptional longevity in humans.
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DOI：
10.1126/science.1190532
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发表时间：
2010-07-01
期刊：
影响因子：
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通讯作者：
Perls, Thomas T
中科院分区：
文献类型：
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作者：
Sebastiani, Paola;Solovieff, Nadia;Perls, Thomas T
健康老龄化被认为反映了环境因素（生活方式选择）和遗传因素的综合影响。为了探索遗传贡献，我们对1055名百岁老人和1267名对照进行了一项异常长寿（EL）的全基因组关联研究。利用这些数据，我们建立了一个包括150个单核苷酸多态性（SNP）的遗传模型，并发现它可以在一组独立的百岁老人和对照组中以77%的准确率预测EL。进一步的计算机分析显示，90%的百岁老人可以分为19个簇，其特征是SNP基因型或遗传特征的不同组合，具有不同的预测价值。证明EL遗传复杂性的不同特征与年龄相关疾病（例如，痴呆、高血压和心血管疾病），并可能有助于将这种复杂的表型分解为健康衰老的亚表型。
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 model that includes 150 single-nucleotide polymorphisms (SNPs) and found that it could predict EL with 77% accuracy in an independent set of centenarians and controls. 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.