While genome-wide association studies have identified susceptibility variants for numerous traits, their combined utility for predicting broad measures of health, such as mortality, remains poorly understood. We used data from the UK Biobank to combine polygenic risk scores (PRS) for 13 diseases and 12 mortality risk factors into sex-specific composite PRS (cPRS). These cPRS were moderately associated with all-cause mortality in independent data within the UK Biobank: the estimated hazard ratios per standard deviation were 1.10 (95% confidence interval: 1.05, 1.16) and 1.15 (1.10, 1.19) for women and men, respectively. Differences in life expectancy between the top and bottom 5% of the cPRS were estimated to be 4.79 (1.76, 7.81) years and 6.75 (4.16, 9.35) years for women and men, respectively. These associations were substantially attenuated after adjusting for non-genetic mortality risk factors measured at study entry (i.e., middle age for most participants). The cPRS may be useful in counseling younger individuals at higher genetic risk of mortality on modification of non-genetic factors.

尽管全基因组关联研究已经确定了许多性状的易感性变异，但它们对预测广泛的健康指标（如死亡率）的综合效用仍然知之甚少。我们使用了来自英国生物银行的数据，将针对13种疾病和12种死亡风险因素的多基因风险评分（PRS）组合为针对性别的复合PRS（cPRS）。这些cPRS在UK Biobank的独立数据中与全因死亡率有中等程度的关联：女性和男性的每个标准差的估计危险比分别为1.10（95％置信区间：1.05，1.16）和1.15（1.10，1.19）。 。男性和女性cPRS的最高5％和最低5％之间的预期寿命差异分别为4.79（1.76，7.81）岁和6.75（4.16，9.35）岁。在调整了研究进入时测得的非遗传性死亡风险因素（即，大多数参与者的中年年龄）后，这些关联大大减弱了。cPRS可能在咨询因非遗传因素改变而具有较高遗传死亡风险的年轻个体中很有用。