A novel Synthetic phenotype association study approach reveals the landscape of association for genomic variants and phenotypes.
A novel Synthetic phenotype association study approach reveals the landscape of association for genomic variants and phenotypes.
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DOI：
10.1016/j.jare.2022.04.004
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发表时间：
2022-12
影响因子：
10.7
通讯作者：
Bilyeu, Kristin D.
中科院分区：
文献类型：
--
作者：
Skrabisova, Maria;Dietz, Nicholas;Zeng, Shuai;Chan, Yen On;Wang, Juexin;Liu, Yang;Biova, Jana;Joshi, Trupti;Bilyeu, Kristin D.
这项研究提出了额外的后GWAS评估标准。准确度用作变体位置和表型之间的直接对应性的量度。每个基因组变体位置都可以用作GWAS中的合成表型。SPAS揭示了基因组变异的关联景观。合成表型利用重新测序的数据集信息。全基因组关联研究（GWAS）鉴定基因组中的标记变体，这些标记变体由于其与致病突变（CM）的连锁不平衡（LD）关系而与表型在统计学上相关。当具有表型的低密度基因分型登录面板和重新测序的数据登录面板都可用时，标记变体可以帮助CM发现中的GWAS后挑战。我们的目标是确定额外的GWAS评估标准，以评估基因组变异和表型之间的对应关系，并对局部关联景观进行更深入的分析。我们在GWAS中使用基因组变异位置作为合成表型，我们将其命名为“合成表型关联研究”（SPAS）。SPAS的极端情况是我们称之为“反向GWAS”，其中我们使用克隆大豆基因的CM位置。我们开发并验证了准确度概念，作为变量位置和表型之间对应关系的度量。SPAS方法表明，用作合成表型的相关变体的基因型状态使我们能够探索标记变体和CM之间的关系，并且进一步地，利用CM作为逆GWAS中的合成表型照亮了关联的前景。我们实现了一个策划的接入面板的准确度计算的在线准确度计算工具（AccuTool）作为大豆基因鉴定的资源。我们用三个大豆克隆基因的例子证明了我们的概念。作为我们的发现的结果，我们设计了增强的“GWAS到基因”分析（合成表型到CM策略，SP2CM）。使用SP2CM，我们确定了一个新基因的CM。SP2CM策略利用合成表型和对应的准确性计算提供了重要的信息，以帮助研究人员在CM发现。这项工作的影响是更有效地评估GWAS协会的景观。
This study proposes additional post-GWAS evaluation criteria. Accuracy serves as a measure of direct correspondence between variant positions and phenotypes. Every genomic variant position can be used as a Synthetic phenotype in GWAS. SPAS reveals the landscape of association for genomic variants. Synthetic phenotype leverages resequenced data set information. Genome-Wide Association Studies (GWAS) identify tagging variants in the genome that are statistically associated with the phenotype because of their linkage disequilibrium (LD) relationship with the causative mutation (CM). When both low-density genotyped accession panels with phenotypes and resequenced data accession panels are available, tagging variants can assist with post-GWAS challenges in CM discovery. Our objective was to identify additional GWAS evaluation criteria to assess correspondence between genomic variants and phenotypes, as well as enable deeper analysis of the localized landscape of association. We used genomic variant positions as Synthetic phenotypes in GWAS that we named “Synthetic phenotype association study” (SPAS). The extreme case of SPAS is what we call an “Inverse GWAS” where we used CM positions of cloned soybean genes. We developed and validated the Accuracy concept as a measure of the correspondence between variant positions and phenotypes. The SPAS approach demonstrated that the genotype status of an associated variant used as a Synthetic phenotype enabled us to explore the relationships between tagging variants and CMs, and further, that utilizing CMs as Synthetic phenotypes in Inverse GWAS illuminated the landscape of association. We implemented the Accuracy calculation for a curated accession panel to an online Accuracy calculation tool (AccuTool) as a resource for gene identification in soybean. We demonstrated our concepts on three examples of soybean cloned genes. As a result of our findings, we devised an enhanced “GWAS to Genes” analysis (Synthetic phenotype to CM strategy, SP2CM). Using SP2CM, we identified a CM for a novel gene. The SP2CM strategy utilizing Synthetic phenotypes and the Accuracy calculation of correspondence provides crucial information to assist researchers in CM discovery. The impact of this work is a more effective evaluation of landscapes of GWAS associations.
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影响因子：
5.3
作者：
Gillman JD;Tetlow A;Lee JD;Shannon JG;Bilyeu K
通讯作者：
Bilyeu K
影响因子：
3.7
作者：
Ferreira Filho, Diogenes;de Sousa Bueno Filho, Julio Silvio;Conceicao Meirelles, Sarah Laguna
通讯作者：
Conceicao Meirelles, Sarah Laguna
大豆驯化过程中控制开花和成熟的同源PRR基因的逐步选择
影响因子：
30.8
作者：
Lu, Sijia;Dong, Lidong;Kong, Fanjiang
通讯作者：
Kong, Fanjiang
与驯化相关的破荚抗性是由大豆中的 NAC 基因介导的
影响因子：
16.6
作者：
Dong, Yang;Yang, Xia;Wang, Yin-Zheng
通讯作者：
Wang, Yin-Zheng
影响因子：
5.8
作者：
Bradbury, Peter J.;Zhang, Zhiwu;Buckler, Edward S.
通讯作者：
Buckler, Edward S.