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新方法提升多基因风险评分
作者:小柯机器人 发布时间:2020/12/2 21:25:22

近日,美国哈佛大学Soumya Raychaudhuri及其研究组使用新方法提升了多基因风险评分。相关论文于2020年11月30日在线发表于国际学术期刊《自然—遗传学》。

通过汇总5,345个表观遗传数据集,研究人员预测了245个细胞类型中142个转录因子的结合模式,并构建了707个细胞类型特异性IMPACT调控注释资源。然后,研究人员划分了欧洲(平均n≈189,000)和东亚(平均n≈157,000)起源的111个全基因组关联的常见SNP遗传力。IMPACT注释捕获了种群之间一致的SNP遗传力,表明了共享功能变异的优先级。

通过IMPACT进行的不同优先级排序使得分析的所有21种表型从欧洲人到东亚人的多基因风险评分提高(R2平均相对增加49.9%)。这项研究确定了诸如IMPACT之类的功能注释对于提高遗传数据分析的关键作用。

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

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex