Analysis of polygenic risk score usage and performance in diverse human populations
Analysis of polygenic risk score usage and performance in diverse human populations
复制标题
DOI：
10.1038/s41467-019-11112-0
复制
发表时间：
2019-07-25
影响因子：
16.6
通讯作者：
Domingue, B.
中科院分区：
文献类型：
--
作者：
Duncan, L.;Shen, H.;Domingue, B.
使用欧洲血统样本的历史趋势阻碍了医学遗传学研究，包括使用多基因评分，这是遗传风险的个人水平指标。我们分析了多基因评分研究的前十年（2008-2017年，含），发现67%的研究仅包括欧洲血统的参与者，另有19%仅包括东亚血统的参与者。只有3.8%的研究是在非洲人，西班牙人或土著人的队列中进行的。我们发现，欧洲血统来源的多基因评分的预测性能在非欧洲血统样本中较低（例如非洲血统样本：t =-5.97，df = 24，p = 3.7 x 10（-6）），我们证明了方法选择对全球人群多基因评分分布的影响。这些发现强调了在将多基因评分应用于非欧洲血统的队列时，需要改进连锁不平衡和变异频率的治疗，并支持在不同人群中进行大规模GWAS的基本原理。
A historical tendency to use European ancestry samples hinders medical genetics research, including the use of polygenic scores, which are individual-level metrics of genetic risk. We analyze the first decade of polygenic scoring studies (2008-2017, inclusive), and find that 67% of studies included exclusively European ancestry participants and another 19% included only East Asian ancestry participants. Only 3.8% of studies were among cohorts of African, Hispanic, or Indigenous peoples. We find that predictive performance of European ancestry-derived polygenic scores is lower in non-European ancestry samples (e.g. African ancestry samples: t = -5.97, df = 24, p = 3.7 x 10(-6)), and we demonstrate the effects of methodological choices in polygenic score distributions for worldwide populations. These findings highlight the need for improved treatment of linkage disequilibrium and variant frequencies when applying polygenic scoring to cohorts of non-European ancestry, and bolster the rationale for large-scale GWAS in diverse human populations.