基因水平的关联分析方法
收稿日期: 2013-03-15
修回日期: 2013-06-17
网络出版日期: 2013-09-25
基金资助
浙江省自然科学基金项目(编号：Y2100240), 宁波市自然科学基金项目(编号：2009A610142), 浙江省卫生厅基金项目(编号：2009A183)和宁波大学胡岚优秀博士基金资助
Advances on gene-based association analysis
Received date: 2013-03-15
Revised date: 2013-06-17
Online published: 2013-09-25
全基因组关联研究(Genome wide association study, GWAS)已经在国内外的医学遗传学研究中得到广泛应用, 但是GWAS数据中所蕴含的与多基因复杂性状疾病机制相关的丰富信息尚未得到深度挖掘。近年来, 研究者采用生物网络分析和生物通路分析等生物信息学和生物统计学手段分析GWAS数据, 并探索潜在的疾病机制。生物网络分析和生物通路分析主要是以基因为单位进行的, 因此必须在分析前将基因上全部或者部分单个单核苷酸多态性(Single nucleotide polymorphism, SNP)的遗传关联结果综合起来, 即基因水平的关联分析。基因水平的关联分析需要考虑单个SNP的遗传关联、基因上SNP数量和SNP之间的连锁不平衡结构等多种因素, 因此不仅在遗传学的概念上也在统计方法方面具有一定的复杂性和挑战性。文章对基因水平的关联分析的研究进展、原理和应用进行了综述。
罗旭红 刘志芳 董长征 . 基因水平的关联分析方法[J]. 遗传, 2013 , 35(9) : 1065 -1071 . DOI: 10.3724/SP.J.1005.2013.01065
Genome-wide association studies (GWAS) have been widely used for hunting the susceptibility genes for common diseases in the past years; however, the abundant information for the disease mechanism based on the GWAS data has not been fully mined. Recently, some researchers focused on the biological network and pathway analysis for the GWAS data to explore the potential disease mechanism. Since genes are the basic units for the biological network and pathway, the genetic effects from all or part of single nucleotide polymorphisms (SNPs) in the genes should be integrated into genetic scores, which are so-called “gene-based association analysis”. Gene-based association analysis takes into account some important factors such as genetic effects of the SNPs, the number of the SNPs in the genes and the linkage disequilibrium structure of the SNPs. In this review, we will focus on the progress, principle and application of gene-based association analysis.
[1] Han JW, Zheng HF, Cui Y, Sun LD, Ye DQ, Hu Z, Xu JH, Cai ZM, Huang W, Zhao GP, Xie HF, Fang H, Lu QJ, Xu JH, Li XP, Pan YF, Deng DQ, Zeng FQ, Ye ZZ, Zhang XY, Wang QW, Hao F, Ma L, Zuo XB, Zhou FS, Du WH, Cheng YL, Yang JQ, Shen SK, Li J, Sheng YJ, Zuo XX, Zhu WF, Gao F, Zhang PL, Guo Q, Li B, Gao M, Xiao FL, Quan C, Zhang C, Zhang Z, Zhu KJ, Li Y, Hu DY, Lu WS, Huang JL, Liu SX, Li H, Ren YQ, Wang ZX, Yang CJ, Wang PG, Zhou WM, Lv YM, Zhang AP, Zhang SQ, Lin D, Li Y, Low HQ, Shen M, Zhai ZF, Wang Y, Zhang FY, Yang S, Liu JJ, Zhang XJ. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet, 2009, 41(11): 1234–1237.<\P>
[2] Sun LD, Cheng H, Wang ZX, Zhang AP, Wang PG, Xu JH, Zhu QX, Zhou HS, Ellinghaus E, Zhang FR, Pu XM, Yang XQ, Zhang JZ, Xu A-E, Wu RN, Xu LM, Peng L, Helms CA, Ren YQ, Zhang C, Zhang SM, Nair RP, Wang HY, Lin GS, Stuart PE, Fan X, Chen G, Tejasvi T, Li P, Zhu J, Li ZM, Ge HM, Weichenthal M, Ye WZ, Zhang C, Shen SK, Yang BQ, Sun YY, Li SS, Lin Y, Jiang JH, Li CT, Chen RX, Cheng J, Jiang X, Zhang P, Song WM, Tang J, Zhang HQ, Sun L, Cui J, Zhang LJ, Tang B, Huang F, Qin Q, Pei XP, Zhou AM, Shao LM, Liu JL, Zhang FY, Du WD, Franke A, Bowcock AM, Elder JT, Liu JJ, Yang S, Zhang XJ. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet, 2010, 42(11): 1005–1009.<\P>
[3] Yue WH, Wang HF, Sun LD, Tang FL, Liu ZH, Zhang HX, Li WQ, Zhang YL, Zhang Y, Ma CC, Du B, Wang LF, Ren YQ, Yang YF, Hu XF, Wang Y, Deng W, Tan LW, Tan YL, Chen Q, Xu GM, Yang GG, Zuo Xb, Yan H, Ruan YY, Lu TL, Han X, Ma XH, Wang Y, Cai LW, Jin C, Zhang HY, Yan J, Mi WF, Yin XY, Ma WB, Liu Q, Kang L, Sun W, Pan CY, Shuang M, Yang FD, Wang CY, Yang JL, Li KQ, Ma X, Li LJ, Yu X, Li QZ, Huang X, Lv LX, Li T, Zhao GP, Huang W, Zhang XJ, Zhang D. Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nat Genet, 2011, 43(12): 1228–1231.<\P>
[4] Chu X, Pan CM, Zhao SX, Liang J, Gao GQ, Zhang XM, Yuan GY, Li CG, Xue LQ, Shen M, Liu W, Xie F, Yang SY, Wang HF, Shi JY, Sun WW, Du WH, Zuo CL, Shi JX, Liu BL, Guo CC, Zhan M, Gu ZH, Zhang XN, Sun F, Wang ZQ, Song ZY, Zou CY, Sun WH, Guo T, Cao HM, Ma JH, Han B, Li P, Jiang H, Huang QH, Liang L, Liu LB, Chen G, Su Q, Peng YD, Zhao JJ, Ning G, Chen Z, Chen JL, Chen SJ, Huang W, Song HD, The China Consortium for the Genetics of Autoimmune Thyroid Disease. A genome-wide association study identifies two new risk loci for Graves' disease. Nat Genet, 2011, 43(9): 897–901.<\P>
[5] Lu X, Wang L, Chen SF, He L, Yang XL, Shi YY, Cheng J, Zhang L, Gu CC, Huang JF, Wu TC, Ma YT, Li JX, Cao J, Chen JC, Ge DL, Fan ZJ, Li Y, Zhao LC, Li HF, Zhou XY, Chen LY, Liu DH, Chen JP, Duan XF, Hao YC, Wang LG, Lu FH, Liu ZD, Yao CL, Shen C, Pu XD, Yu L, Fang XH, Xu LH, Mu JJ, Wu XP, Zheng RP, Wu NQ, Zhao Q, Li Y, Liu XL, Wang MQ, Yu DH, Hu DS, Ji X, Guo DS, Sun DL, Wang QQ, Yang Y, Liu FC, Mao QX, Liang XH, Ji JF, Chen PP, Mo XB, Li DJ, Chai GP, Tang YD, Li XD, Du ZH, Liu XH, Dou CL, Yang ZL, Meng QJ, Wang D, Wang RP, Yang J, Schunkert H, Samani NJ, Kathiresan S, Reilly MP, Erdmann J, Peng XZ, Wu XG, Liu DP, Yang YJ, Chen RS, Qiang BQ, Gu DF. Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. Nat Genet, 2012, 44(8): 890–894.<\P>
[6] Wang K, Li MY, Bucan M. Pathway-based approaches for analysis of genomewide association studies. Am J Hum Genet, 2007, 81(6): 1278–1283.<\P>
[7] Peng G, Luo L, Siu H, Zhu Y, Hu PF, Hong SJ, Zhao JY, Zhou XD, Reveille JD, Jin L, Amos CI, Xiong MM. Gene and pathway-based second-wave analysis of genome-wide association studies. Eur J Hum Genet, 2010, 18(1): 111–117.<\P>
[8] Jia PL, Zheng SY, Long JR, Zheng W, Zhao ZM.
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