综述

全基因组关联研究的深度分析策略

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  • 安徽医科大学皮肤病研究所, 合肥 230032

收稿日期: 2010-08-16

  修回日期: 2010-10-19

  网络出版日期: 2011-02-25

基金资助

国家“863”计划项目(编号:2007AA02Z161)资助

Research strategies for the next step of genome-wide association study

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  • Institute of Dermatology of Anhui Medical University, Hefei 230032, China

Received date: 2010-08-16

  Revised date: 2010-10-19

  Online published: 2011-02-25

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。

本文引用格式

权晟,张学军 . 全基因组关联研究的深度分析策略[J]. 遗传, 2011 , 33(2) : 100 -108 . DOI: 10.3724/SP.J.1005.2011.00100

Abstract

Since 2005, genome-wide association studies (GWAS) have yielded an unprecedented number of complex dis-eases/traits-associated variants. Recently, scientists have focused on performing further analysis by utilizing the ge-nome-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 dif-ferent 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 of complex diseases/traits. We reviewed these strategies and methods, as well as their diffi-culty and challenge. Meanwhile, we presented a brief framework of GWAS next step to readers.

参考文献

[1] the Wellcome Trust Case Control Consortium. Ge-nome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 2007, 447(7145): 661-678.

[2] Thomson W, Barton A, Ke XY, Eyre S, Hinks A, Bowes J, Donn R, Symmons D, Hider S, Bruce IN, Wilson AG, Marinou I, Morgan A, Emery P, YEAR Consortium, Carter A, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Strachan D, Worthington J. Rheumatoid arthritis association at 6q23. Nat Genet, 2007, 39(12): 1431-1433.

[3] Barton A, Thomson W, Ke XY, Eyre S, Hinks A, Bowes J, Plant D, Gibbons LJ, Wellcome Trust Case Control Con-sortium, YEAR Consortium, BIRAC Consortium, Wilson AG, Bax DE, Morgan AW, Emery P, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Worthington J. Rheumatoid arthritis susceptibility loci at chromosomes 10p15, 12q13 and 22q13. Nat Genet, 2008, 40(10): 1156-1159.

[4] Eeles RA, Kote-Jarai Z, Al Olama AA, Giles GG, Guy M, Severi G, Muir K, Hopper JL, Henderson BE, Haiman CA, Schleutker J, Hamdy FC, Neal DE, Donovan JL, Stanford JL, Ostrander EA, Ingles SA, John EM, Thibodeau SN, Schaid D, Park JY, Spurdle A, , The UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, The UK ProtecT Study Collaborators, The PRACTICAL Consor-tium, Easton DF. Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat Genet, 2009, 41(10): 1116-1121.

[5] Sun LD, Cheng H, Wang ZX, Zhang AP, Wang PG, Xu JH, Zhu QX, Zhou HS, Ellinghaus E, Zhang FR, Pu XM . Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet. 2010, 42(11): 1005–1009.

[6] Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, Hu T. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet, 2008, 40(5): 638-645.

[7] Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS. Genome-wide association defines more than 30 distinct sus-ceptibility loci for Crohn's disease. Nat Genet, 2008, 40(8): 955-962.

[8] De Jager PL, Jia XM, Wang J, de Bakker PIW, Ottoboni L, Aggarwal NT, Piccio L, Raychaudhuri S, Tran D, Aubin C, Briskin R, Romano S, International MS Genetics Consor-tium, Baranzini SE, McCauley JL, Pericak-Vance MA, Haines JL, Gibson RA, Naeglin Y, Uitdehaag B, Matthews PM, Kappos L, Polman C, McArdle WL, Strachan DP, Evans D, Cross AH, Daly MJ, Compston A, Sawcer SJ, Weiner HL, Hauser SL, Hafler DA, Oksenberg JR. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis sus-ceptibility loci. Nat Genet, 2009, 41(7): 776-782.

[9] Raychaudhuri S, Remmers EF, Lee AT, Hackett R, Guiducci C, Burtt NP, Gianniny L, Korman BD, Padyukov L, Kurreeman FAS, Chang M, Catanese JJ, Ding B, Wong S, van der Helm-van Mil AHM, Neale BM, Coblyn J, Cui J, Tak PP, Wolbink GJ, Crusius JBA, van der Horst-Bruinsma IE, Criswell LA, Amos CI, Seldin MF, Kastner DL, Ardlie KG, Alfredsson L, Costenbader KH, Altshuler D, Huizinga TWJ, Shadick NA, Weinblatt ME, de Vries N, Worthington J, Seielstad M, Toes REM, Karl-son EW, Begovich AB, Klareskog L, Gregersen PK, Daly MJ, Plenge RM. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet, 2008, 40(10): 1216-1223.

[10] Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MCC, Lubbe S, Chandler I. Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat Genet, 2008, 40(12): 1426-1435.

[11] Ioannidis JP, Patsopoulos NA, Evangelou E. Heterogeneity in meta-analyses of genome-wide association investigations. PLoS One, 2007, 2(9): e841.

[12] Pei YF, Li J, Zhang L, Papasian CJ, Deng HW. Analyses and comparison of accuracy of different genotype impu
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