Poor trans-ancestry portability of polygenic risk scores is a consequence of Eurocentric genetic studies and limited knowledge of shared causal variants. Leveraging regulatory annotations may improve portability by prioritizing functional over tagging variants. We constructed a resource of 707 cell-type-specific IMPACT regulatory annotations by aggregating 5,345 epigenetic datasets to predict binding patterns of 142 transcription factors across 245 cell types. We then partitioned the common SNP heritability of 111 genome-wide association study summary statistics of European (average n ≈ 189,000) and East Asian (average n ≈ 157,000) origin. IMPACT annotations captured consistent SNP heritability between populations, suggesting prioritization of shared functional variants. Variant prioritization using IMPACT resulted in increased trans-ancestry portability of polygenic risk scores from Europeans to East Asians across all 21 phenotypes analyzed (49.9% mean relative increase in R²). Our study identifies a crucial role for functional annotations such as IMPACT to improve the trans-ancestry portability of genetic data.

多基因风险评分的跨血统可移植性差是欧洲中心遗传学研究和共享因果变异知识有限的结果。利用监管注释可以通过将功能优先于标记变体来提高可移植性。我们通过聚合 5,345 个表观遗传数据集来预测 245 种细胞类型中 142 种转录因子的结合模式，构建了 707 个细胞类型特异性 IMPACT 调节注释资源。然后，我们划分了欧洲（平均n  ≈ 189,000）和东亚（平均n ≈ 157,000) 原产地。IMPACT 注释捕获了群体之间一致的 SNP 遗传力，表明共享功能变体的优先级。使用 IMPACT 的变体优先级导致在分析的所有 21 种表型中从欧洲人到东亚人的多基因风险评分的跨血统可移植性增加（R ²平均相对增加 49.9% ）。我们的研究确定了功能注释（如 IMPACT）在提高遗传数据的跨血统可移植性方面的关键作用。