小柯机器人

近日，美国加州大学洛杉矶分校Bogdan Pasaniuc等研究人员合作发现，基因评分的准确性在不同的遗传血统连续体中有别。这一研究成果于2023年5月17日在线发表在国际学术期刊《自然》上。

研究人员利用大型的、多样化的洛杉矶生物库（ATLAS，n=36778）和英国生物库（UKBB，n=487409），表明在所有考虑的人群中，即使在传统上被称为“同质”的基因祖先中，多基因评分（PGS）的准确性也会沿着基因祖先的连续体逐个下降。从PGS训练数据中得到的遗传距离（GD）的连续测量很好地反映了这种下降趋势： 在84个性状中，GD和PGS准确性之间的皮尔逊相关性为-0.95。当把在UKBB中被标记为英国白人的个体所训练的PGS模型应用于ATLAS中具有欧洲血统的个体时，相对于最接近的十分位数，最远的GD十分位数的个体的准确性要低14%。

值得注意的是，具有西班牙裔美国人血统的最接近的GD十分位数的个体的PGS表现与具有欧洲血统的最远的GD十分位数相似。在84个性状中，有82个性状的GD与PGS估计值本身明显相关，进一步强调了在PGS解释中纳入连续的遗传血统的重要性。这些结果强调，在考虑PGS时，需要从离散的遗传祖先集群转向遗传祖先的连续体。

据介绍，PGS在不同人群中的移植性有限（例如，按遗传和/或健康的社会决定因素），妨碍了其公平使用。PGS的可移植性通常使用单一的总体人口统计数字（如R2）来评估，忽略了人口中个体间的差异。

附：英文原文

Title: Polygenic scoring accuracy varies across the genetic ancestry continuum

Author: Ding, Yi, Hou, Kangcheng, Xu, Ziqi, Pimplaskar, Aditya, Petter, Ella, Boulier, Kristin, Priv, Florian, Vilhjlmsson, Bjarni J., Olde Loohuis, Loes M., Pasaniuc, Bogdan

Issue&Volume: 2023-05-17

Abstract: Polygenic scores (PGSs) have limited portability across different groupings of individuals (for example, by genetic ancestries and/or social determinants of health), preventing their equitable use1,2,3. PGS portability has typically been assessed using a single aggregate population-level statistic (for example, R2)4, ignoring inter-individual variation within the population. Here, using a large and diverse Los Angeles biobank5 (ATLAS, n=36,778) along with the UK Biobank6 (UKBB, n=487,409), we show that PGS accuracy decreases individual-to-individual along the continuum of genetic ancestries7 in all considered populations, even within traditionally labelled ‘homogeneous’ genetic ancestries. The decreasing trend is well captured by a continuous measure of genetic distance (GD) from the PGS training data: Pearson correlation of 0.95 between GD and PGS accuracy averaged across 84 traits. When applying PGS models trained on individuals labelled as white British in the UKBB to individuals with European ancestries in ATLAS, individuals in the furthest GD decile have 14% lower accuracy relative to the closest decile; notably, the closest GD decile of individuals with Hispanic Latino American ancestries show similar PGS performance to the furthest GD decile of individuals with European ancestries. GD is significantly correlated with PGS estimates themselves for 82 of 84 traits, further emphasizing the importance of incorporating the continuum of genetic ancestries in PGS interpretation. Our results highlight the need to move away from discrete genetic ancestry clusters towards the continuum of genetic ancestries when considering PGSs.

DOI: 10.1038/s41586-023-06079-4

Source: https://www.nature.com/articles/s41586-023-06079-4

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