新方法提升多基因風險評分
作者：
小柯機器人發布時間：2020/12/2 21:25:22
近日，美國哈佛大學Soumya Raychaudhuri及其研究組使用新方法提升了多基因風險評分。相關論文於2020年11月30日在線發表於國際學術期刊《自然—遺傳學》。
通過匯總5,345個表觀遺傳數據集，研究人員預測了245個細胞類型中142個轉錄因子的結合模式，並構建了707個細胞類型特異性IMPACT調控注釋資源。然後，研究人員劃分了歐洲（平均n≈189,000）和東亞（平均n≈157,000）起源的111個全基因組關聯的常見SNP遺傳力。IMPACT注釋捕獲了種群之間一致的SNP遺傳力，表明了共享功能變異的優先級。
通過IMPACT進行的不同優先級排序使得分析的所有21種表型從歐洲人到東亞人的多基因風險評分提高（R2平均相對增加49.9％）。這項研究確定了諸如IMPACT之類的功能注釋對於提高遺傳數據分析的關鍵作用。
附：英文原文
Title: Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements
Author: Tiffany Amariuta, Kazuyoshi Ishigaki, Hiroki Sugishita, Tazro Ohta, Masaru Koido, Kushal K. Dey, Koichi Matsuda, Yoshinori Murakami, Alkes L. Price, Eiryo Kawakami, Chikashi Terao, Soumya Raychaudhuri
Issue&Volume: 2020-11-30
Abstract: 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.
DOI: 10.1038/s41588-020-00740-8
Source: https://www.nature.com/articles/s41588-020-00740-8