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科学家提高基因组精确映射
作者:小柯机器人 发布时间:2020/11/17 16:11:44

美国哈佛大学陈公共卫生学院Alkes L. Price及Omer Weissbrod研究组取得最新进展。他们提出功能性信息复杂性状遗传力的精确映射和多基因定位。该研究于2020年11月16日发表于《自然-遗传学》。

他们提出了PolyFun是一种可计算扩展的框架,可利用整个基因组中的功能注释(而不仅仅是全基因组范围内的重要位点)来提高精确映射的准确性,从而指定诸如SuSiE或FINEMAP精确映射方法的先验概率。在模拟中,PolyFun®+ SuSiE和PolyFun®+ FINEMAP进行了很好的校准,并比未提供功能的同类产品鉴定出> 0.95后因果概率多20%。在对49个英国生物库特征(平均n = 318,000)进行分析时,PolyFun®+ SuSiE确定了3025个精确映射的变异-性状对,其后因果概率> 0.95,与SuSiE相比提高了32%。

他们使用PolyFun + SuSuEE的后平均单SNP遗传力进行多基因定位,构建了最小的普通SNP集,从而解释了50%的普通SNP遗传力。这些集合的大小从28(头发颜色)到3,400(高度)到200万(儿童数量)不等。

总之,PolyFun对功能进行了优先排序,以进行功能跟踪,并提供了对复杂特征架构的见解。

附:英文原文

Title: Functionally informed fine-mapping and polygenic localization of complex trait heritability

Author: Omer Weissbrod, Farhad Hormozdiari, Christian Benner, Ran Cui, Jacob Ulirsch, Steven Gazal, Armin P. Schoech, Bryce van de Geijn, Yakir Reshef, Carla Mrquez-Luna, Luke OConnor, Matti Pirinen, Hilary K. Finucane, Alkes L. Price

Issue&Volume: 2020-11-16

Abstract: Fine-mapping aims to identify causal variants impacting complex traits. We propose PolyFun, a computationally scalable framework to improve fine-mapping accuracy by leveraging functional annotations across the entire genome—not just genome-wide-significant loci—to specify prior probabilities for fine-mapping methods such as SuSiE or FINEMAP. In simulations, PolyFun+SuSiE and PolyFun+FINEMAP were well calibrated and identified >20% more variants with a posterior causal probability >0.95 than identified in their nonfunctionally informed counterparts. In analyses of 49 UK Biobank traits (average n=318,000), PolyFun+SuSiE identified 3,025 fine-mapped variant–trait pairs with posterior causal probability >0.95, a >32% improvement versus SuSiE. We used posterior mean per-SNP heritabilities from PolyFun+SuSiE to perform polygenic localization, constructing minimal sets of common SNPs causally explaining 50% of common SNP heritability; these sets ranged in size from 28 (hair color) to 3,400 (height) to 2 million (number of children). In conclusion, PolyFun prioritizes variants for functional follow-up and provides insights into complex trait architectures.

DOI: 10.1038/s41588-020-00735-5

Source: https://www.nature.com/articles/s41588-020-00735-5

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