Merging multiple vcf files into one

Question

[hpapoli]

Hello,

I have 280 vcf files, each containing about 200 SNPs from a genotyping experiment. I need to merge all these so I can have a final combined vcf where I have all SNPs in all individuals, that is if an individual lacks that SNP, in the combined file it is coded as ./. or .

I am using the following command from vcftools: vcf-merge A.vcf.gz B.vcf.gz C.vcf.gz | bgzip -c > out.vcf.gz

It worked for two files, although it took about 1 hour, now it's been running of 1 day for the whole 280 files. I was wondering if this is the only way of merging a large number of vcf files or if there is any other way to make it more efficient?

Thank you

Answer 1

[Pierre Lindenbaum]

GATK CombineVariants https://www.broadinstitute.org/gatk/gatkdocs/org_broadinstitute_gatk_tools_walkers_variantutils_CombineVariants.php

find . -name "*.vcf.gz" > input.list

java -jar GenomeAnalysisTK.jar \
       -T CombineVariants \
       -R ref.fa
       --variant input.list
       -o out.vcf
       -genotypeMergeOptions REQUIRE_UNIQUE

[Nikleotide]

Thanks for the answer Pierre. Quick question on the matter of reference genome though, let's say we have a collection of VCF files from different times and thus different reference genomes, is there an easy solution with the combinevariants command ro should we lift all the non-compatible ones to a single reference genome and then combine them?