Transcriptome-wide association studies: a view from Mendelian randomization

作     者：Huanhuan Zhu Xiang Zhou Huanhuan Zhu;Xiang Zhou

作者机构：Department of BiostatisticsUniversity of MichiganAnn ArborMl 48109USA Center for Statistical GeneticsUniversity of MichiganAnn ArborMl 48109USA 

出 版 物：《Quantitative Biology》 (定量生物学（英文版）)

年 卷 期：2021年第9卷第2期

页      面：107-121页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：the National Institutes of Health(NIH)Grants RO1HG009124 and the National Science Foundation(NSF)Grant DMS1712933 

主　　题：transcriptome-wide association studies genome-wide association studies expression mapping studies 

摘      要：Background:Genome-wide association studies(GWASs)have identified thousands of genetic variants that are associated with many complex ***,their biological mechanisms remain largely ***-wide association studies(TWAS)have been recently proposed as an invaluable tool for investigating the potential gene regulatory mechanisms underlying variant-trait ***,TWAS integrate GWAS with expression mapping studies based on a common set of variants and aim to identify genes whose GReX is associated with the *** methods have been developed for performing TWAS and/or similar integrative *** such method has a different modeling assumption and many were initially developed to answer different biological ***,it is not straightforward to understand their modeling property from a theoretical ***:We present a technical review on thirteen TWAS ***,we show that these methods can all be viewed as two-sample Mendelian randomization(MR)analysis,which has been widely applied in GWASs for examining the causal effects of exposure on *** different TWAS methods from an MR perspective provides us a unique angle for understanding their benefits and *** systematically introduce the MR analysis framework,explain how features of the GWAS and expression data influence the adaptation of MR for TWAS,and re-interpret the modeling assumptions made in different TWAS methods from an MR *** finally describe future directions for TWAS methodology ***:We hope that this review would serve as a useful reference for both methodologists who develop TWAS methods and practitioners who perform TWAS analysis.