Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome-wide association scans of two age-adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers^1,2 in European-descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein-coding SNPs, PhenoAgeAccel-rs429358 (APOE e4 determinant) (p=1.50 × 10^-72); BioAgeAccel-rs7412 (APOE e2 determinant) (p=3.16 × 10^-60). Interestingly, we observed inverse APOE e2 and e4 associations and unique pathway enrichments when comparing the two biological age measures. Genes associated with BioAgeAccel were enriched in lipid related pathways, while genes associated with PhenoAgeAccel showed enrichment for immune system, cell function, and carbohydrate homeostasis pathways, suggesting the two measures capture different aging domains. Our study reaffirms that aging patterns are heterogenous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition.

中文翻译：

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两种生物学年龄测度的遗传关联指向不同的衰老表型。

在预测各种衰老结果时，生物年龄的测量优于时序年龄，但对遗传易感性知之甚少。我们对来自英国生物库的欧洲血统参与者的临床生化标记^1,2估计了两种年龄调整的生物学年龄测量值（PhenoAgeAcceleration和BioAgeAcceleration）进行了全基因组关联扫描。在APOE基因中发现了最强的信号，该信号由两个主要的编码蛋白质的SNP PhenoAgeAccel-rs429358（APOE e4决定簇）标记（p = 1.50×10 ^-72）；BioAgeAccel-rs7412（APOE e2决定簇）（p = 3.16×10 ^-60）。有趣的是，当比较两种生物学年龄指标时，我们观察到了反向的APOE e2和e4关联以及独特的途径富集。与BioAgeAccel相关的基因富含脂质相关途径，而与PhenoAgeAccel相关的基因则富含免疫系统，细胞功能和碳水化合物稳态途径，表明这两种方法捕获了不同的衰老域。我们的研究重申，个体之间的衰老模式是异质的，一个人的衰老方式可能部分归因于遗传易感性。