Department of Obstetrics and Gynecology, Columbia University, New York City, New York, USA.
Department of Pharmacology, College of Medicine, Hallym University, Chuncheon, Gangwon, Korea.
Aging Cell. 2023 Oct;22(10):e13962. doi: 10.1111/acel.13962. Epub 2023 Aug 22.
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.
全基因组关联研究 (GWAS) 已经确定了染色体 9p21.3 区域是与多种与年龄相关的疾病相关的遗传热点。该区域的常见遗传变异与多种特征相关，包括冠状动脉疾病、癌症和糖尿病。众所周知，百岁老人患这些疾病的风险较低，发病时间也较晚。为了研究这种疾病风险的规避是否涉及 9p21.3 区域遗传风险的降低，我们对一个阿什肯纳兹犹太百岁老人队列（百岁老人：n=450，健康对照：n=500）进行了该区域的测序。与癌症、青光眼、CAD 和 T2D 相关的风险等位基因在百岁老人中明显减少。此外，风险和非风险基因型与两个不同的低频变异谱相关联，分别在对照组和百岁老人中富集。我们的研究结果提供了证据，表明极端长寿队列与 9p21.3 区域多种与年龄相关的疾病的总体较低风险相关。
