RAREMETALWORKER command reference

Useful Links

Here are some useful links to key pages:

• RAREMETALWORKER documentation
• RAREMETALWORKER method
• RAREMETALWORKER special topics
• FAQ

List of Options

 Options:
       Input Files : --ped [], --dat [], --vcf [], --dosage, --noeof
      Output Files : --prefix [], --LDwindow [1000000], --zip, --thin,
                     --labelHits
        VC Options : --vcX, --separateX
     Trait Options : --makeResiduals, --inverseNormal, --traitName []
     Model Options : --recessive, --dominant
    Kinship Source : --kinPedigree, --kinGeno, --kinFile [], --kinxFile [],
                     --kinSave
   Kinship Options : --kinMaf [0.05], --kinMiss [0.05]
      Chromosome X : --xLabel [X], --xStart [2699520], --xEnd [154931044],
                     --maleLabel [1], --femaleLabel [2]
         PhoneHome : --noPhoneHome, --phoneHomeThinning [100]

Input Files

--ped

• --ped takes a string of your MERLIN format PED file name.

--dat

• --ped takes a string of your MERLIN format DAT file name.

--vcf

• --vcf takes a string of your VCF file name.

--dosage

• When --dosage is issued in command line, RAREMETALWORKER reads dosage from your VCF file.
• --dosage must be used with --vcf option.
• Description of dosage format in a VCF file can be found in dosage.

--noeof

• If you VCF file does not have the BGZF EOF markers, you should use --noeof option to let RAREMETALWORKER skip checking the BGZF EOF markers at the end of the file.
• Please see BGZF EOF for more details.

Output Files

--prefix

• --prefix takes a value of a string as the prefix of your output files.
• For a full list of output files generated by RAREMETALWORKER, please refer to output.

--LDwindow

• --LDwindow takes a integer value as the size of the moving window.
• RAREMETALWORKER generates LD matrices between a current marker that it is working on and all markers within this window.
• The default size is 1 million bases.
• For more information about the LD matrix, please refer to LD matrix.

--zip

• By issuing --zip, RAREMETALWORKER compress the summary statistics and LD matrices generated automatically, using gzip.

--thin

• If --thin is issued, then RAREMETALWORKER generates QQ plots and Manhattan plots with less resolution (points), to make the pdf files smaller in size.

--labelHits

• If --thin is issued, then RAREMETALWORKER automatically label the loci that are above a threshold.
• The threshold is calculated using Bonferroni correction (0.05/N, where N is the total number of polymorphic markers).

VC Options

--vcX

• --vcX option has to be used with --kinPedigree (when pedigree kinship is used), or --kinGeno (when genomic relationship matrix is estimated), or --kinFile ( when GRM is read from a file).
• Using --vcX option let RAREMETALWORKER fit a linear mixed model to analyze chromosome X, using both autosomal kinship and chromosome X kinship.

--separateX

• --separateX option must be used with --vcX option.
• Using --separateX option requests RAREMETALWORKER to fit a linear mixed model using only chromosome X kinship for analyses of chromosome X markers.

Please refer to method and technical details for more explanation.

Trait Options

--makeResiduals

• If --makeResiduals is used, then covariates are adjusted before fitting linear models using residuals.

--inverseNormal

• If --inverseNormal is used, but not with --makeResiduals, then trait values are inverse normalized before fitting linear models.
• If --inverseNormal and --makeResiduals are used together, then covariates are adjusted and inverse normalized residuals are used to fit linear models.

--traitName

• --traitName takes a string of the trait name that you want to analyze.
• If this option is not used, then all traits included in PED/DAT files are analyzed.

Model Options

--recessive

• If --recessive is used, then RAREMETALWORKER generates recessive results in addition to the additive results.
• The set of association results generated by default can be found in recessive output.
• A separate pdf file with QQ and Manhattan plots based on recessive results is generated with name yourprefix.traitname.recessive.plots.pdf.

--dominant

• If --dominant is used, then RAREMETALWORKER generates recessive results in addition to the additive results.
• The set of association results generated by default can be found in dominant output.
• A separate pdf file with QQ and Manhattan plots based on recessive results is generated with name yourprefix.traitname.dominant.plots.pdf.

PhoneHome

• --prefix is optional.
• If --prefix is not specified, the output file names will be:

 traitname.singlevar.score.txt
 traitname.singlevar.cov.txt

• Otherwise, the output file names are:

 prefix.traitname.singlevar.score.txt
 prefix.traitname.singlevar.cov.txt

• --LDwindow specifies the length of the window that LD Matrix should be generated upon each variant. The default is 1MB.
• --zip gives users the option of writing compressed files (bgzip compressed) automatically for convenient sharing.
• --thin tells RMW to thin points when generating QQ plot and Manhattan plots, so the file size is smaller.
• --labelHits tells RMW to to label the hits using pvalue threshold 0.05/(#of variants tested) with gene name, based on human genome build 19.

VC Options

• When --vcShared and --vcX are specified, RMW knows that you want to fit shared environment and/or chromosome X variance component together with genetic component and non-shared environment.
• When --makeResiduals is specified, RMW understands covariates should be read from PED/DAT file. Covariates are modeled as fixed effects.

Trait Options

• --makeResiduals tells RMW to adjust the covariates and analyze residuals instead of the original phenotypes. If either --kinGeno or --kinPedigree option is used, then a variance component model will be fit based on residuals. If the --inverseNormal option is also used, then the residuals will be quantile normalized before fitting variance component model.
• --traitName is created for situations when you have many traits saved in your PED and DAT file, but you are interested in one or a few of them. It can read a file ending with .txt with each trait of interest in a separate line, or trait names separated with "/". An example to handle one trait or multiple traits is in the following:

  --traitName LDL
  --traitName LDL/HDL/TG
  --traitName traitsOfInterest.txt

• If --traitName is not used, all traits in PED/DAT file will be analyzed.

Model Options

• additive model is used in RMW as default.
• --recessive allows additional association results (pvalue, effect size, and standard error) generated using recessive model. If VCF file is used, then non-reference allele is considered the recessive allele. If PED/DAT files are used for genotype, then minor allele is considered the recessive allele.
• --dominant allows additional association results (pvalue, effect size, and standard error) generated using dominant model. If VCF file is used, then non-reference allele is considered the dominant allele. If PED/DAT files are used for genotype, then minor allele is considered the dominant allele.
• --recessive and --dominant options can be used together.
• Recessive and dominant results are stored in separate files.

Kinship Source

• --kinPedigree allows RMW to generate kinship matrix from pedigree, when pedigree information is available.
• --kinGeno informs RMW to generate kinship matrix from all available variants that pass the criteria, specified in --kinMaf and --kinMiss options. The default will take variants with MAF>0.05 and genotype missing rate <0.05.
• --kinGeno option can NOT be used with --kinPedigree or --kinFile option. Only one of three options or none of them can be used in the same run.
• --kinFile let RMW read in a kinship matrix from a file. The first row of the kinship file has to be the sample IDs included in the kinship file. If a sample of interest is not included in the kinship file, fatal error will occur and the program will be terminated. A sample of interest is a sample that is phenotyped and has all covariates measured when --makeResiduals is specified.
• --kinSave allows you to save the kinship matrix.

Kinship Options

• --kinMiss and --kinMaf should be used with --kinGeno together.
• --kinMiss specifies the maximum genotype missing rate when calculating kinship from genotypes. The default is 0.05.
• --kinMaf specifies the minimum minor allele frequency used when calculating kinship from genotypes. The default is 0.05.

Chromosome X

• --xLabel should have a value of a string which specifies how variants on chromosome X are coded. The default is "X".
• --xStart and --xEnd specifies the start and end of non-pseudo-autosomal regions on chromosome X. These options should be specified when --vcX is used.
• The default for --xStart is 2699520 and default for --xEnd is 154931044, according to NCBI genome build 37.

Please refer to the following for the analysis of X-linked variants ANALYZING CHROMOSOME X.

PhoneHome Parameters

See PhoneHome for more information on how PhoneHome works and what it does.

• --noPhoneHome disables PhoneHome. PhoneHome is enabled by default based on the thinning parameter.

• --phoneHomeThinning (0-100) adjusts the frequency of PhoneHome.
  • By default, --phoneHomeThinning is set to 50, running 50% of the time.
  • PhoneHome will only occur if the run's random number modulo 100 is less than the --phoneHomeThinning value.
  • N/A if --noPhoneHome is set.