NAME¶

QTLtools rtc-union - Find the union of QTLs from independent datasets

SYNOPSIS¶

QTLtools rtc-union --vcf [in.vcf|in.vcf.gz|in.bcf|in.bed.gz] ... --bed quantifications.bed.gz ... --hotspots hotspots_b37_hg19.bed --results qtl_results_files.txt ... [OPTIONS]

DESCRIPTION¶

This mode finds the best molQTL (may or may not be genome-wide significant) in each region flanked by recombination hotspots (coldspot), if there was a molQTL in the same coldspot in one dataset. First we map all the significant molQTLs in all of the datasets to coldspots. Subsequently if certain datasets do not have a significant molQTL in a given coldspot for a given phenotype, we then take the most significant variant associated with that phenotype in that coldspot, for all the missing datasets.

OPTIONS¶

--vcf [in.vcf|in.bcf|in.vcf.gz|in.bed.gz] ...

Genotypes in VCF/BCF format, or another molecular phenotype in BED format. If there is a DS field in the genotype FORMAT of a variant (dosage of the genotype calculated from genotype probabilities, e.g. after imputation), then this is used as the genotype. If there is only the GT field in the genotype FORMAT then this is used and it is converted to a dosage. If a single file is provided then all datasets are assumed to have the same genotypes, and all datasets' samples are all included in this file. If multiple files are provided for each dataset, then all --vcf, --bed, --cov, and --results files MUST be in the same order. E.g if the first vcf file is from dataset1, then the first bed, cov, and results files must also be from dataset1. REQUIRED.

--bed quantifications.bed.gz ...

Molecular phenotype quantifications in BED format for each of the datasets. All --vcf, --bed, --cov, and --results files MUST be in the same order. E.g if the first vcf file is from dataset1, then the first bed, cov, and results files must also be from dataset1. REQUIRED.

--results significant_qtls.txt ...

Results file with the QTLs in each of the datasets. All --vcf, --bed, --cov, and --results files MUST be in the same order. E.g if the first vcf file is from dataset1, then the first bed, cov, and results files must also be from dataset1. REQUIRED.

--hotspots recombination_hotspots.bed

Recombination hotspots in BED format. REQUIRED.

--out-suffix suffix

If provided output files will be suffixed with this.

--cov covariates.txt

Covariates to correct the phenotype data with for each of the datasets. All --vcf, --bed, --cov, and --results files MUST be in the same order. E.g if the first vcf file is from dataset1, then the first bed, cov, and results files must also be from dataset1.

--force

If the output file exists, overwrite it.

--normal

Rank normal transform the phenotype data so that each phenotype is normally distributed. RECOMMENDED.

--conditional

molQTLs contain independent signals so execute the conditional analysis.

--window integer

Size of the cis window flanking each phenotype's start position. DEFAULT=1000000. RECOMMENDED=1000000.

--pheno-col integer

1-based phenotype id column number. DEFAULT=1

--geno-col integer

1-based genotype id column number. DEFAULT=8

--rank-col integer

1-based conditional analysis rank column number. Only relevant if --conditional is in effect. DEFAULT=12

--best-col integer

1-based phenotype column number Only relevant if --conditional is in effect. DEFAULT=21

--chunk integer1 integer2

For parallelization. Divide the data into integer2 number of chunks and process chunk number integer1. Chunk 0 will print a header. Mutually exclusive with --region. Minimum number of chunks has to be at least the same number of chromosomes in the --bed file.

--region chr:start-end

Genomic region to be processed. E.g. chr4:12334456-16334456, or chr5. Mutually exclusive with --chunk.

OUTPUT FILE¶

output file

Space separated output file with the following columns.

1	Column showing that this is a rtc-union result. Always __UNION__
2	The phenotype ID
3	The genotype ID. This can say __UNION_FILLER_MAX_INDEP__, __UNION_FILLER_MISS_GENO__, or __UNION_FILLER_MISS_PHENO__ which are fillers for missing cases in one of the datasets.
4	The rank of the best variant in this coldspot. If this was discovered in the rtc-union run then this would be -1, and if there was already a significant variant in this coldspot then a different value.
5	Dummy field indicating that this is the best hit per rank
6	The p-value of the association. Will be 0 if this was already significant in the dataset
7	The coldspot ID
8	The coldspot region

EXAMPLE¶

o

Find the union of 3 datasets, correcting for technical covariates, and rank normal transforming the phenotypes with 20 jobs on a compute cluster (qsub needs to be changed to the job submission system used [bsub, psub, etc...]):

for j in $(seq 1 20); do

echo "QTLtools rtc-union --bed dataset1.bed.gz dataset2.bed.gz dataset3.bed.gz --vcf dataset1.bcf dataset2.bcf dataset3.bcf --cov dataset1.covariates.txt dataset2.covariates.txt dataset3.covariates.txt --results dataset1.txt dataset2.txt dataset3.txt --hotspots hotspots_b37_hg19.bed --normal --conditional --chunk $j 20 --out-suffix .chunk.$j.20.txt" | qsub

done

SEE ALSO¶

QTLtools(1)

QTLtools website: <https://qtltools.github.io/qtltools>

BUGS¶

Versions up to and including 1.2, suffer from a bug in reading missing genotypes in VCF/BCF files. This bug affects variants with a DS field in their genotype's FORMAT and have a missing genotype (DS field is .) in one of the samples, in which case genotypes for all the samples are set to missing, effectively removing this variant from the analyses.

Please submit bugs to <https://github.com/qtltools/qtltools>

CITATION¶

Ongen H, Brown AA, Delaneau O, et al. Estimating the causal tissues for complex traits and diseases. Nat Genet. 2017;49(12):1676-1683. doi:10.1038/ng.3981 <https://doi.org/10.1038/ng.3981>

AUTHORS¶

Halit Ongen (halitongen@gmail.com), Olivier Delaneau (olivier.delaneau@gmail.com)