GWAS: 曼哈頓圖,QQ plot 圖,膨脹系數( manhattan、Genomic Inflation Factor)


畫曼哈頓圖和QQ plot 首推R包“qqman”,簡約方便。下面具體介紹以下。

一、畫曼哈頓圖

install.packages("qqman")

library(qqman)

  

1、准備包含SNP, CHR, BP, P的文件gwasResults(如果沒有zscore可以不用管),如下所示:

2、上代碼,如下所示:

manhattan(gwasResults)

  

plot of chunk unnamed-chunk-4

如果覺得不夠美觀,考慮添加一下參數:

manhattan(gwasResults, main = "Manhattan Plot", ylim = c(0, 10), cex = 0.6, cex.axis = 0.9, col = c("blue4", "orange3"), suggestiveline = F, genomewideline = 6, chrlabs = c(1:20, "P", "Q"))

  

plot of chunk unnamed-chunk-5

二、畫 QQ plot 圖

直接上代碼:

qq(gwasResults$P)

  

plot of chunk unnamed-chunk-12

同樣的,還可以修改參數,美觀一下:

qq(gwasResults$P, main = "Q-Q plot of GWAS p-values", xlim = c(0, 7), ylim = c(0,    12), pch = 18, col = "blue4", cex = 1.5, las = 1)

  

plot of chunk unnamed-chunk-13

 

三、計算膨脹系數(Calculating Genomic Inflation Factor)

 

如果數據類型為Z值,則膨脹系數為:

z = gwasResults$zscore
lambda = round(median(z^2) / 0.454, 3)

  

如果數據類型是P值,則膨脹系數為:

p_value=gwasResults$P

z = qnorm(p_value/ 2)

lambda = round(median(z^2, na.rm = TRUE) / 0.454, 3)

  

​如果數據類型是CHISQ值,則膨脹系數為:

z = gwasResults$CHISQ

lambda = round(median(z^2, na.rm = TRUE) / 0.454, 3)

  

 

#關於0.454的由來:

#qchisq(0.5, 1)

#[1] 0.4549364

 

膨脹系數lambda的解讀:

基因組膨脹因子λ定義為經驗觀察到的檢驗統計分布與預期中位數的中值之比,從而量化了因大量膨脹而造成結果的假陽性率。換句話說,λ定義為得到的卡方檢驗統計量的中值除以卡方分布的預期中值。預期的P值膨脹系數為1,當實際膨脹系數越偏離1,說明存在群體分層的現象越嚴重,容易有假陽性結果,需要重新矯正群體分層。



 

參考鏈接:

https://www.biostars.org/p/43328/

https://cran.r-project.org/web/packages/qqman/vignettes/qqman.html

https://en.wikipedia.org/wiki/Population_stratification

chrome-extension://cdonnmffkdaoajfknoeeecmchibpmkmg/static/pdf/web/viewer.html?file=https%3A%2F%2Fpersonal.broadinstitute.org%2Fchrisnc%2Fothers%2FGWAS_Smith_MethMolBiol09.pdf

chrome-extension://cdonnmffkdaoajfknoeeecmchibpmkmg/static/pdf/web/viewer.html?file=http%3A%2F%2Fwww3.stat.sinica.edu.tw%2Fsisg2015%2Fdownload%2Fhandout%2FS1-notes.pdf


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