VCF-merge fails due to tabix not producing .tbi files I'm trying to use vcf-merge to combine 2 exome capture vcf files (~250K and ~330K in size) before trying it on all 96 samples. I'd appreciate any advice on the best way to do that! I've detailed what I've tried below. My issue seems to be with using tabix to convert the files to .tbi format.

Step 1: BGZIP

So far, I've zipped the files without issue:

bgzip sample1.vcf
bgzip sample2.vcf


which produces: 

sample1.vcf.gz
sample2.vcf.gz


Step 2: TABIX

When I try to use this command:tabix -h -p vcf sample1.vcf.gz the stderr is: Region 536999277..536999278 cannot be stored in a tbi index. Try using a csi index with min_shift = 14, n_lvls &gt;= 6. tbx_index_build failed: sample1.vcf.gz

Using the -C option which works:

tabix -C -h -p vcf sample1.vcf.gz
tabix -C -h -p vcf sample2.vcf.gz


which produces:
    sample1.vcf.gz.csi
    sample2.vcf.gz.csi

Step 3: VCF-MERGE

When I use this command: vcf-merge sample1.vcf.gz.csi sample2.vcf.gz.csi &gt; out.vcf.gz the merge fails, and I get this stderr:

Broken VCF header, no column names? at /usr/share/perl5/Vcf.pm line 172, &lt;__ANONIO__&gt; line 1. Vcf::throw(Vcf4_2=HASH(0x5645a760bc38), "Broken VCF header, no column names?") called at /usr/share/perl5/Vcf.pm line 867 VcfReader::_read_column_names(Vcf4_2=HASH(0x5645a760bc38)) called at /usr/share/perl5/Vcf.pm line 602 VcfReader::parse_header(Vcf4_2=HASH(0x5645a760bc38)) called at /usr/bin/vcf-merge line 183 main::init_cols(HASH(0x5645a761f438), Vcf4_2=HASH(0x5645a760b248)) called at /usr/bin/vcf-merge line 279 main::merge_vcf_files(HASH(0x5645a761f438)) called at /usr/bin/vcf-merge line 12


If I exclude the tabix files, the merge still fails and the stderr says: The column names not tab-separated? Could not load .tbi index of sample1.vcf.gz. The command exited with an error. Is the file tabix indexed?

Any suggestions on how I can correctly merge these files?
You should go with the CSI index as it seems like the BAI indexes cannot handle chromosomes longer than 2^29.

Your problem is that you're trying to merge the index files using vcf-merge. You should merge the VCF files, not the .csi index files.