中国卒中杂志2025，Vol.20Issue(6)：664-674,11.DOI:10.3969/j.issn.1673-5765.2025.06.002
全基因组关联分析标准化流程的构建与扩展应用
Development and Extended Applications of Standardized Processes for Genome-Wide Association Studies
摘要
Abstract
Objective To develop standardized workflow for GWAS and multi-omics analysis frameworks,providing an efficient analytical pipeline for pharmaceutical reverse engineering of cerebrovascular diseases using multi-omics cohorts. Methods A modular analysis system was constructed based on international GWAS quality control standards and multi-omics integration strategies.Pre-GWAS data quality control module:this module performed stringent quality control on sample and variant call rates,population genetic structure and stratification,and kinship.In the population composed of qualified samples,genetic variants with a minor allele frequency＞0.5％ were retained for GWAS.Association analysis module:using software such as PLINK,SAIGE,and Regenie,GWAS was performed utilizing generalized linear models and generalized linear mixed models.The quality of GWAS was evaluated by the genome inflation coefficient and quantile-quantile plots.The module was tested using whole-genome sequencing and clinical data from the China national stroke registry Ⅲ.Multi-omics analysis module:this module integrated polygenic risk score,cross-cohort meta-analysis,Mendelian randomization,and colocalization analysis procedures,providing support for molecular mechanism interpretation and target screening using GWAS results. Results The pre-GWAS data quality control module established in this study conducts pre-GWAS quality control and assessment from the aspects of genetic data quality and population genetics.After quality control,9632 and 7265 samples were included in the GWAS of baseline TG levels and 3-month post-stroke mortality phenotypes,respectively.The GWAS results showed that the trends of Manhattan plots obtained from different software were similar.However,compared to PLINK and Regenie,SAIGE software offered more appropriate correction and relatively robust statistical testing,especially when case-control samples were biased.In the multi-omics analysis module,standardized analysis processes including polygenic risk score,meta-analysis,Mendelian randomization,and colocalization analysis were developed to enable in-depth exploration of GWAS results. Conclusions The GWAS standardization processes established in this study are characterized by modularity and high scalability,enabling comprehensive analysis of complex phenotypes and multi-omics data.These processes provide a methodological foundation for exploration of pharmaceutical reverse engineering based on genetic association.关键词
全基因组关联分析/多组学/卒中/药物研发/生物信息学Key words
Genome-wide association study/Multi-omics/Stroke/Drug development/Bioinformatics分类
医药卫生引用本文复制引用
许喆,石延枫,张杰,姜明慧,刘阳,李昊,廖晓凌,程丝..全基因组关联分析标准化流程的构建与扩展应用[J].中国卒中杂志,2025,20(6):664-674,11.基金项目
国家重点研发计划(2022YFE0209600)国家自然科学基金(82471304)中国科协青年人才托举工程(2023QNRC001) （2022YFE0209600）
