Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan
Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan
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DOI：
10.1038/s41591-020-0785-8
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发表时间：
2020-03-23
期刊：
影响因子：
82.9
通讯作者：
Okada, Yukinori
中科院分区：
文献类型：
--
作者：
Sakaue, Saori;Kanai, Masahiro;Okada, Yukinori
交叉生物库分析显示，高血压和肥胖的多基因风险评分（PRS）与较短的寿命相关，作为PRS可以确定影响长期健康结果的因果风险因素的原理证明。虽然多基因风险评分（PRS）准备通过预测先天健康风险转化为临床实践（1），有必要制定一项利用遗传学来优先考虑可改变的风险因素的战略（2）。为此，我们与三个全球生物库（n（总数）= 675，898; BioBank Japan（n = 179，066），UK Biobank（n = 361，194）和FinnGen（n = 135，638））合作调查了复杂性状的遗传易感性与人类寿命的关联。与观察性研究相比，辨别因果关系可能很困难，PRS可以帮助识别影响人类寿命的驱动生物标志物。高收缩压PRS与寿命缩短（风险比= 1.03[1.02-1.04]，P-meta = 3.9 x 10（-13））和父母寿命缩短（风险比= 1.06[1.06-1.07]，P = 2.0 x 10（-86））跨种族相关。肥胖PRS对日本和欧洲个体的寿命有明显影响（BMI的P异质性= 9.5 x 10（-8））。血压和肥胖对寿命的因果影响得到了孟德尔随机研究的进一步支持。除了基因型-表型相关性，我们的trans-biobank研究提供了一个新的价值，优先考虑的风险因素，可能是潜在的医疗目标，以改善人口健康的PRS。
Cross-biobank analysis reveals that polygenic risk scores (PRS) for hypertension and obesity are associated with shorter lifespan, serving as a proof-of-principle that PRS could pinpoint causal risk factors that affect long-term health outcomes.While polygenic risk scores (PRSs) are poised to be translated into clinical practice through prediction of inborn health risks(1), a strategy to utilize genetics to prioritize modifiable risk factors driving heath outcome is warranted(2). To this end, we investigated the association of the genetic susceptibility to complex traits with human lifespan in collaboration with three worldwide biobanks (n(total) = 675,898; BioBank Japan (n = 179,066), UK Biobank (n = 361,194) and FinnGen (n = 135,638)). In contrast to observational studies, in which discerning the cause-and-effect can be difficult, PRSs could help to identify the driver biomarkers affecting human lifespan. A high systolic blood pressure PRS was trans-ethnically associated with a shorter lifespan (hazard ratio = 1.03[1.02-1.04], P-meta = 3.9 x 10(-13)) and parental lifespan (hazard ratio = 1.06[1.06-1.07], P = 2.0 x 10(-86)). The obesity PRS showed distinct effects on lifespan in Japanese and European individuals (P-heterogeneity = 9.5 x 10(-8) for BMI). The causal effect of blood pressure and obesity on lifespan was further supported by Mendelian randomization studies. Beyond genotype-phenotype associations, our trans-biobank study offers a new value of PRSs in prioritization of risk factors that could be potential targets of medical treatment to improve population health.