Wang Han, Li Xiang, Li Teng, Li Zhe, Sham Pak Chung, Zhang Yan Dora
College of Science, China Agricultural University, Beijing, China.
Department of Statistics and Actuarial Science, School of Computing and Data Science, The University of Hong Kong, Hong Kong SAR, China.
Genome Biol. 2025 Feb 4;26(1):21. doi: 10.1186/s13059-025-03485-x.
Transcriptome-wide association study (TWAS) has emerged as a powerful tool for translating the myriad variations identified by genome-wide association studies (GWAS) into regulated genes in the post-GWAS era. While integrating annotation information has been shown to enhance power, current annotation-assisted TWAS tools predominantly focus on epigenomic annotations. When including more annotations, the assumption of a positive correlation between annotation scores and SNPs' effect sizes, as adopted by current methods, often falls short. Here, we propose MAAT expanding the horizons of existing TWAS studies, generating a new model incorporating multiple annotations into TWAS and a new metric indicating the most important annotation.
全转录组关联研究(TWAS)已成为后全基因组关联研究(GWAS)时代将GWAS所识别的众多变异转化为受调控基因的强大工具。虽然整合注释信息已被证明可增强效能,但当前基于注释的TWAS工具主要侧重于表观基因组注释。当纳入更多注释时,当前方法所采用的注释分数与单核苷酸多态性(SNP)效应大小之间呈正相关的假设往往并不成立。在此,我们提出MAAT,拓展现有TWAS研究的视野,生成一个将多个注释纳入TWAS的新模型以及一个指示最重要注释的新指标。