Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Road, Stanford, CA, 94305, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 667 Huntington Ave, Kresge 505, Boston, MA, 02115, USA.
Nat Commun. 2019 Jul 25;10(1):3328. doi: 10.1038/s41467-019-11112-0.
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 × 10), 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.
使用欧洲血统样本的历史趋势阻碍了医学遗传学研究，包括多基因评分的使用，这是个体遗传风险的衡量标准。我们分析了多基因评分研究的第一个十年（2008-2017 年，包括在内），发现 67%的研究仅包括欧洲血统的参与者，另有 19%的研究仅包括东亚血统的参与者。只有 3.8%的研究是在非洲、西班牙裔或原住民群体的队列中进行的。我们发现，欧洲血统衍生的多基因评分在非欧洲血统样本中的预测性能较低（例如非洲血统样本：t=-5.97，df=24，p=3.7×10），并且我们展示了多基因评分分布在全球人群中的方法选择的影响。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，需要改进对连锁不平衡和变异频率的处理，并且为在不同人类群体中进行大规模 GWAS 提供了合理依据。
