GWAS学习笔记——imputation的含义 (Truth of Imputation)
Do not imput onther's sin to yourself
scheme of imputation in statistics
GWAS学习笔记——imputation的含义 (Truth of Imputation)
by Baoyu
7月份参加了Fudan主办的首期GWAS研修班，对国内外GWAS有了系统、深入的感知。学习过程中，需要精准地理解一些重要概念，才能避免一知半解。
GWAS相关重要的名词有Effect heterogeneity，Pooling，ReplicationJointPooled analysis，Geographic variation，Hierarchical Clustering，imputation，marginal effects，Manhattan Forest，GWAS consortium (如Genetic Association Information Network, GAIN)。这次班上不少老师把Manhattan Forest改称为Pudong Forest，Pudong楼群的高度和密度都不亚于Manhattan)，呵呵。
GWAS研究中，imputation前承高通量测序，下启数据分析；对缺失数据的imputation是进行数据分析的前提，重要性不言而喻。
Impute愿意是归罪,归咎,归因,非难,诋毁。Merian-Webster辞典的解释既是此义：
Main Entry: impute
Function: transitive verb
Inflected Form:imputed ; imputing
Etymology: Middle English inputen, from Latin imputare, from in- + putare to consider Date: 14th century
1: to lay the responsibility or blame for often falsely or unjustly
2: to credit to a person or a cause: ATTRIBUTE *our vices as well as our virtues have been imputed to bodily derangement B. N. Cardozo
synonyms see ASCRIBE.
统计遗传学中意为预测、插补，由已知的基因型预测未知的基因型并对缺失的数据进行补缺，如这句：
This imputation method uses the dense genotype data available from the HapMap CEU samples and the linkage disequilibrium (LD) relationships of the SNPs to impute (predict) genotypes for a large number of SNPs that were not measured experimentally in our Finnish cases and controls.
Statistical genetics中imputation 的三个主要作用：
Allows testing of untyped variation ，
Allows easy combination of data across genotyping platforms ，
Provides complete data for analysis with multiple SNPs.
实现imputation的常用软件：
1. IMPUTE
Developed by Jonathan Marchini
Nature Genetics, Advance online publication
http://www.stats.ox.ac.uk/~marchini/#software
2. Mach 1.0, Markov Chain Haplotyping
Developed by Goncalo Abecasis
http://www.sph.umich.edu/csg/abecasis/MACH/
附件1是U Michigen 的小牛Scott对imputation等分析方法的一个介绍。
附件2是Eric E Schadt (Rosetta Inpharmatics)实验室最近在BMC Genetis上一篇题为GWAS中插补（imputation）准确度及对关联分析统计效力的影响，值得一读。
附件1 Scott_Handling and analyzing data of GWAS
附件2 09 Accuracy of genome-wide imputation of untyped markers and...