Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK.
MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Am J Hum Genet. 2024 Jun 6;111(6):1006-1017. doi: 10.1016/j.ajhg.2024.04.009. Epub 2024 May 3.
We present shaPRS, a method that leverages widespread pleiotropy between traits or shared genetic effects across ancestries, to improve the accuracy of polygenic scores. The method uses genome-wide summary statistics from two diseases or ancestries to improve the genetic effect estimate and standard error at SNPs where there is homogeneity of effect between the two datasets. When there is significant evidence of heterogeneity, the genetic effect from the disease or population closest to the target population is maintained. We show via simulation and a series of real-world examples that shaPRS substantially enhances the accuracy of polygenic risk scores (PRSs) for complex diseases and greatly improves PRS performance across ancestries. shaPRS is a PRS pre-processing method that is agnostic to the actual PRS generation method, and as a result, it can be integrated into existing PRS generation pipelines and continue to be applied as more performant PRS methods are developed over time.
我们提出了 shaPRS 方法,该方法利用特征之间或跨血统的共享遗传效应的广泛多效性,来提高多基因评分的准确性。该方法使用两种疾病或血统的全基因组汇总统计数据来提高 SNP 处的遗传效应估计值和标准误差,这些 SNP 在两个数据集之间具有效应的同质性。当存在显著的异质性证据时,保留来自与目标人群最接近的疾病或人群的遗传效应。我们通过模拟和一系列实际示例表明,shaPRS 极大地提高了复杂疾病的多基因风险评分(PRS)的准确性,并大大提高了跨血统的 PRS 性能。shaPRS 是一种 PRS 预处理方法,它与实际的 PRS 生成方法无关,因此,它可以集成到现有的 PRS 生成管道中,并随着时间的推移继续应用,因为更具性能的 PRS 方法不断发展。