全基因组关联研究地深度分析策略.PDFVIP

HEREDITAS (Beijing) 2011 年 2 月, 33(2): 1―9 ISSN 0253-9772 综述 DOI: 10.3724/SP.J.1005.2011.00000 全基因组关联研究的深度分析策略 权晟, 张学军 , 230032 摘要: 2005 年至今, 全基因组关联研究(Genome-wide association study, GWAS)发现了大量复杂疾病/性状相关 变异。近来, 科学家们关注的焦点又集中在了如何利用GWAS 数据进行深入分析, 期待发现更多复杂疾病/ 性状 的易感基因。一些新的策略和方法已经被尝试应用到复杂疾病/ 性状GWAS 的后续研究中, 例如深入分析GWAS 数据; 鉴定新的复杂疾病/ 性状易感基因/位点; 国际合作和 Meta 分析; 易感区域精细定位及测序; 多种疾病共 同易感基因研究; 以及基因型填补, 基于通路的关联分析, 基因-基因、基因-环境交互作用和上位研究等。这些 策略和方法的应用弥补了经典 GWAS 的一些不足之处, 进一步推动了人类对复杂疾病/性状遗传机制的认识。 文章对上述研究的策略、方法以及所面临的问题和挑战进行了综述, 为读者描绘了GWAS 后期工作的一个简要 框架。 关键词: 全基因组关联研究; 复杂疾病; 性状; 易感基因 Research strategies for the next step of genome-wide association study QUAN Cheng, ZHANG Xue-Jun Institute of Dermatology of Anhui Medical University , Hefei 230032, China Abstract: Since 2005, genome-wide association studies (GWAS) have yielded an unprecedented number of complex diseases/traits-associated variants. Recently, scientists have focused on performing further analysis by utilizing the genome-wide genotyping data to identify more susceptibility genes of complex diseases/traits. Many strategies and methods have been applied in the following GWAS, such as screening other new susceptibility genes/loci for complex diseases/traits, international collaboration and meta-analysis, fine mapping and resequencing, studies on shared susceptibility genes in different diseases, imputation methods, pathway analysis, gene-gene and gene-environment interaction, and epistasis study and so on. The application of these strategies and methods compensates the limitation of the traditional GWAS and provides new insights into genetics basis