Package for PCA on post-imputation dosage genotype data for GWAS (minimac/Michigan imputation server)

Question

[Oak]

Dear all,

I want to do PCA on post-imputation dosage data to adjust for population stratification (for GWA). Are there any packages that allow SNP pruning and principal component analysis on post-imputation dosage data? [particularly minimac /"Michigan imputation server" outputs]

Many thanks for your replies beforehand,

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My thoughts on potential approaches:

1. My impression is that bigsnpr (PMID: 32415959) can use dosage data, however:

• Still relies on plink hardcalls (bed files) for SNP pruning

• It seems to be adapt to BGEN files. Likely there needs to be tweaking to extract and feed the dosage from minimac vcf files.

1. I could also use hardcalls all the way for PCA calculation, then use those PCs for GWA on dosage data. I suspect this might be justifiable because use of either dosage or hardcalls did not seem to have much of an impact on PC calculation in this study: PMID: 32415959 > Results > section 4.5 > last 3 sentences.

2. I could use genotype chip PCs instead of post-imputation dose PCs, I have put that as a separate thread already.

Answer 1

[chrchang523]

plink 2.0 can handle this easily.