Genetic associations for two biological age measures point to distinct aging phenotypes.

Genetic associations for two biological age measures point to distinct aging phenotypes.
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两种生物年龄指标的遗传关联指向不同的衰老表型。

DOI:
10.1111/acel.13376
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发表时间:
2021-06
期刊:
影响因子:
7.8
通讯作者:
Levine ME
Levine ME
中科院分区:
生物学1区
文献类型:
--
作者:
Kuo CL;Pilling LC;Liu Z;Atkins JL;Levine ME

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生物学年龄的措施优于实际年龄在预测各种老化的结果,但鲜为人知的是关于遗传易感性。我们对两种年龄调整的生物学年龄指标(表型加速和生物学加速)进行了全基因组关联扫描,这些指标是从临床生物化学标志物估计的(Levine et al.,2018; Levine,2013)来自英国生物银行的欧洲血统参与者。在APOE基因中发现了最强的信号,由两个主要的蛋白质编码SNP标记,PhenoGlycoprotein-rs 429358(APOE e4决定簇)(p = 1.50 × 10−72); BioGlycoprotein-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测量时,我们观察到反向APOE e2和e4关联和独特的途径富集。与BioGlucose Accel相关的基因在脂质相关途径中富集,而与PhenoGlucose Accel相关的基因显示出免疫系统,细胞功能和碳水化合物稳态途径的富集,表明这两种措施捕获不同的衰老域。我们的研究重申,衰老模式在个体之间是异质的,一个人衰老的方式可能部分归因于遗传倾向。在英国生物库样本中使用两种先前建立的衰老指标进行了衰老率差异的全基因组关联研究。结果表明,一个与脂质代谢和血压相关的基因有关,而另一个与免疫功能相关的基因有关。APOE e4在反映脂质年龄的测量中与更快的衰老相关,但矛盾的是,在反映免疫功能和炎症的测量中与衰老减少相关。
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 (Levine et al., 2018; Levine, 2013) 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 heterogeneous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition. A genome‐wide association study for differences in aging rates was performed in the UK Biobank sample using two previously established aging measures. Results suggest that one was associated with genes involved in lipid metabolism and blood pressure, while the other was associated with genes involved in immune functioning. APOE e4 was associated with faster aging in the measure reflecting lipid age, yet paradoxically, was associated with reduced aging in the measure reflecting immune functioning and inflammation.
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发表时间: 2018-10
期刊: Nature
影响因子: 64.8
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影响因子: 30.8
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