基因组关联研究(GWAS)已将染色体位点9p21.3确定为各种与年龄相关疾病的遗传热点。该位点上的常见遗传变异与冠状动脉疾病、癌症和糖尿病等多种特征相关。百岁老人因其较低的风险和延迟发病时间而被认为是这些疾病的逃避者。为了调查这种逃避疾病风险是否涉及到9p21.3位点遗传风险的减小，我们对一个阿什肯纳齐犹太百岁老人队列进行了该区域的测序(百岁老人: n = 450，健康对照组: n = 500)。与癌症、青光眼、冠状动脉疾病和2型糖尿病相关的风险等位基因在百岁老人中显著减少。此外，风险和非风险基因型与两种不同的低频变异基因型相关，分别在对照组和百岁老人中富集。我们的研究结果表明，在9p21.3位点，极长寿群体与多种年龄相关疾病的风险总体上较低有关。© 2023 The Authors. Aging Cell由解剖学学会和John Wiley & Sons Ltd出版。

Genome-wide association studies (GWAS) have pinpointed the chromosomal locus 9p21.3 as a genetic hotspot for various age-related disorders. Common genetic variants in this locus are linked to multiple traits, including coronary artery diseases, cancers, and diabetes. Centenarians are known for their reduced risk and delayed onset of these conditions. To investigate whether this evasion of disease risks involves diminished genetic risks in the 9p21.3 locus, we sequenced this region in an Ashkenazi Jewish centenarian cohort (centenarians: n = 450, healthy controls: n = 500). Risk alleles associated with cancers, glaucoma, CAD, and T2D showed a significant depletion in centenarians. Furthermore, the risk and non-risk genotypes are linked to two distinct low-frequency variant profiles, enriched in controls and centenarians, respectively. Our findings provide evidence that the extreme longevity cohort is associated with collectively lower risks of multiple age-related diseases in the 9p21.3 locus.© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.