Parameters & Options
Comprehensive reference for all command-line parameters in SAIGE-QTL.
Table of contents
createSparseGRM.R
Creates a sparse genetic relationship matrix (GRM). Optional preprocessing step for computational efficiency.
| Parameter | Type | Default | Description |
--plinkFile | character | ”” | PLINK file prefix (without extension) |
--bedFile | character | ”” | PLINK bed file (if not using --plinkFile) |
--bimFile | character | ”” | PLINK bim file (if not using --plinkFile) |
--famFile | character | ”” | PLINK fam file (if not using --plinkFile) |
GRM Options
| Parameter | Type | Default | Description |
--relatednessCutoff | numeric | 0.125 | Kinship threshold for relatedness (0.125 = second-degree relatives) |
--numRandomMarkerforSparseKin | integer | 2000 | Number of random markers to identify related samples |
--isDiagofKinSetAsOne | logical | FALSE | Set GRM diagonal elements to 1 |
--minMAFforGRM | numeric | 0.01 | Minimum MAF for markers used in GRM |
--maxMissingRateforGRM | numeric | 0.15 | Maximum missing rate for markers used in GRM |
Computation
| Parameter | Type | Default | Description |
--nThreads | integer | 16 | Number of CPU threads |
--memoryChunk | numeric | 2 | Memory chunk size (Gb) |
--outputPrefix | character | ”~/” | Output path and prefix |
step1_fitNULLGLMM_qtl.R
Fits the null Poisson mixed model for eQTL analysis.
Genotype Files
| Parameter | Type | Default | Description |
--plinkFile | character | ”” | PLINK file prefix for GRM construction and variance ratio estimation |
--bedFile | character | ”” | PLINK bed file |
--bimFile | character | ”” | PLINK bim file |
--famFile | character | ”” | PLINK fam file |
Phenotype Files
| Parameter | Type | Default | Description |
--phenoFile | character | ”” | Required. Tab/space-delimited phenotype file with header |
--phenoCol | character | ”” | Required. Phenotype column name (e.g., gene ID) |
--sampleIDColinphenoFile | character | “IID” | Required. Sample ID column name |
--cellIDColinphenoFile | character | ”” | Cell ID column name (for single-cell data) |
--SampleIDIncludeFile | character | ”” | File with sample IDs to include |
Sparse GRM Files
| Parameter | Type | Default | Description |
--sparseGRMFile | character | ”” | Pre-calculated sparse GRM file |
--sparseGRMSampleIDFile | character | ”” | Sample IDs for sparse GRM (no header) |
Additional Matrices
| Parameter | Type | Default | Description |
--VmatFilelist | character | ”” | Comma-separated list of additional covariance matrices |
--VmatSampleFilelist | character | ”” | Sample IDs for each V matrix |
Phenotype and Covariates
| Parameter | Type | Default | Description |
--traitType | character | “binary” | Required. Trait type: “count” (eQTL), “binary”, or “quantitative” |
--covarColList | character | ”” | Comma-separated covariate columns |
--sampleCovarColList | character | ”” | Comma-separated individual-level covariates |
--qCovarColList | character | ”” | Comma-separated categorical covariates (must also be in --covarColList) |
--offsetCol | character | NULL | Offset column (e.g., log total UMI counts) |
--varWeightsCol | character | NULL | Variance weights column |
--isRemoveZerosinPheno | logical | FALSE | Remove zeros from phenotype |
--invNormalize | logical | FALSE | Inverse normalize quantitative traits |
--minCovariateCount | numeric | -1 | Min count for binary covariates (-1 = no filter) |
| Parameter | Type | Default | Description |
--useGRMtoFitNULL | logical | TRUE | Use GRM in null model fitting |
--useSparseGRMtoFitNULL | logical | FALSE | Use sparse GRM for null model |
--useSparseGRMforVarRatio | logical | FALSE | Use sparse GRM for variance ratio estimation |
--relatednessCutoff | numeric | 0 | Kinship threshold for sparse GRM |
--isDiagofKinSetAsOne | logical | FALSE | Set GRM diagonal to 1 |
--minMAFforGRM | numeric | 0.01 | Min MAF for GRM markers |
--maxMissingRateforGRM | numeric | 0.15 | Max missing rate for GRM markers |
Model Fitting
| Parameter | Type | Default | Description |
--tol | numeric | 0.02 | Convergence tolerance |
--maxiter | integer | 20 | Maximum iterations |
--tolPCG | numeric | 1e-5 | PCG convergence tolerance |
--maxiterPCG | integer | 500 | Maximum PCG iterations |
--tauInit | character | “0,0” | Initial tau values (comma-separated) |
--isCovariateOffset | logical | TRUE | Estimate fixed effect coefficients |
--isCovariateTransform | logical | TRUE | Apply QR transformation to covariates |
--skipModelFitting | logical | FALSE | Skip fitting (requires existing model file) |
Variance Ratio Estimation
| Parameter | Type | Default | Description |
--skipVarianceRatioEstimation | logical | FALSE | Skip variance ratio estimation |
--numRandomMarkerforVarianceRatio | integer | 30 | Initial number of random markers (auto-increases) |
--ratioCVcutoff | numeric | 0.001 | CV threshold for variance ratio |
--traceCVcutoff | numeric | 0.0025 | CV threshold for trace estimation |
--nrun | numeric | 30 | Number of runs for trace estimation |
--includeNonautoMarkersforVarRatio | logical | FALSE | Include non-autosomal markers |
Categorical Variance Ratios
| Parameter | Type | Default | Description |
--isCateVarianceRatio | logical | FALSE | Estimate variance ratios by MAC category |
--cateVarRatioMinMACVecExclude | character | “10,20.5” | Lower MAC bounds (comma-separated) |
--cateVarRatioMaxMACVecInclude | character | “20.5” | Upper MAC bounds (comma-separated) |
LOCO (Leave-One-Chromosome-Out)
| Parameter | Type | Default | Description |
--LOCO | logical | TRUE | Apply LOCO approach |
--isLowMemLOCO | logical | FALSE | Output model files by chromosome (reduces memory) |
Output Control
| Parameter | Type | Default | Description |
--outputPrefix | character | ”~/” | Required. Output path and prefix |
--outputPrefix_varRatio | character | ”” | Variance ratio file prefix (defaults to --outputPrefix) |
--IsOverwriteVarianceRatioFile | logical | FALSE | Overwrite existing variance ratio file |
--isStoreSigma | logical | TRUE | Store inverse Sigma matrix |
--isShrinkModelOutput | logical | TRUE | Remove unnecessary objects (reduces file size) |
--isExportResiduals | logical | FALSE | Export residual vectors |
Computation
| Parameter | Type | Default | Description |
--nThreads | integer | 1 | Number of CPU threads |
--memoryChunk | numeric | 2 | Memory chunk size (Gb) |
--SPAcutoff | numeric | 2 | SPA threshold (in SD units) |
Sex-Specific Analysis
| Parameter | Type | Default | Description |
--FemaleOnly | logical | FALSE | Run for females only (requires --sexCol, --FemaleCode) |
--MaleOnly | logical | FALSE | Run for males only (requires --sexCol, --MaleCode) |
--sexCol | character | ”” | Sex column name |
--FemaleCode | character | “1” | Female indicator value |
--MaleCode | character | “0” | Male indicator value |
step2_tests_qtl.R
Performs association tests using the null model from Step 1.
Choose one format:
VCF/BCF Files
| Parameter | Type | Default | Description |
--vcfFile | character | ”” | VCF/BCF file path |
--vcfFileIndex | character | ”” | VCF index (.csi) |
--vcfField | character | “DS” | Field to extract: “DS” (dosage) or “GT” (genotype) |
SAV Files
| Parameter | Type | Default | Description |
--savFile | character | ”” | SAV file path |
--savFileIndex | character | ”” | SAV index (.s1r) |
BGEN Files
| Parameter | Type | Default | Description |
--bgenFile | character | ”” | BGEN file (v1.2, 8-bit compression) |
--bgenFileIndex | character | ”” | BGEN index (.bgi) |
--sampleFile | character | ”” | Sample file for BGEN (required for v≥0.38) |
PLINK Files
| Parameter | Type | Default | Description |
--bedFile | character | ”” | PLINK bed file |
--bimFile | character | ”” | PLINK bim file |
--famFile | character | ”” | PLINK fam file |
--AlleleOrder | character | “alt-first” | Allele order: “alt-first” or “ref-first” |
Variant Selection
| Parameter | Type | Default | Description |
--idstoIncludeFile | character | ”” | File with variant IDs (chr:pos_ref/alt, one per line) |
--rangestoIncludeFile | character | ”” | File with regions (chr, start, end; no header) |
--chrom | character | ”” | Chromosome (required for LOCO or VCF/SAV) |
Quality Filters
| Parameter | Type | Default | Description |
--minMAF | numeric | 0 | Minimum minor allele frequency |
--minMAC | numeric | 0.5 | Minimum minor allele count |
--minInfo | numeric | 0 | Minimum imputation INFO (if --is_imputed_data=TRUE) |
--maxMissing | numeric | 0.15 | Maximum missing rate |
--is_imputed_data | logical | FALSE | Whether data is imputed |
--impute_method | character | “best_guess” | Missing imputation: “best_guess”, “mean”, or “minor” |
--dosage_zerod_cutoff | numeric | 0.2 | Dosage zeroing threshold (for imputed data) |
--dosage_zerod_MAC_cutoff | numeric | 10 | MAC threshold for dosage zeroing |
Step 1 Model Files
Choose one:
Single Phenotype
| Parameter | Type | Default | Description |
--GMMATmodelFile | character | ”” | Model file (.rda) from Step 1 |
--varianceRatioFile | character | ”” | Variance ratio file (.varianceRatio.txt) from Step 1 |
Multiple Phenotypes
| Parameter | Type | Default | Description |
--GMMATmodel_varianceRatio_multiTraits_File | character | ”” | 3-column file: phenotype, model file, variance ratio file |
Single-Variant Tests
| Parameter | Type | Default | Description |
--LOCO | logical | TRUE | Apply LOCO (requires --chrom) |
--SPAcutoff | numeric | 2 | SPA threshold (in SD units) |
--is_Firth_beta | logical | FALSE | Use Firth correction for effect size (binary traits) |
--pCutoffforFirth | numeric | 0.01 | P-value threshold for Firth |
Set-Based Tests
Group File
| Parameter | Type | Default | Description |
--groupFile | character | ”” | Group file with variant sets |
Variant Filters
| Parameter | Type | Default | Description |
--maxMAF_in_groupTest | character | “0.0001,0.001,0.01” | Max MAF for masks (comma-separated) |
--minMAF_in_groupTest_Exclude | character | NULL | Min MAF for masks (comma-separated) |
--maxMAC_in_groupTest | character | “0” | Max MAC for masks (comma-separated) |
--minMAC_in_groupTest_Exclude | character | NULL | Min MAC for masks (comma-separated) |
--annotation_in_groupTest | character | “lof,missense;lof,missense;lof;synonymous” | Annotations (; combines multiple) |
--MACCutoff_to_CollapseUltraRare | numeric | 10 | MAC threshold for collapsing ultra-rare variants |
--minGroupMAC_in_BurdenTest | numeric | 5 | Min MAC for burden test pseudo-marker |
Test Types
| Parameter | Type | Default | Description |
--r.corr | numeric | 0 | Test type: 0=SKAT-O, 1=Burden only |
--is_SKATO | logical | FALSE | Perform SKAT-O test |
--weights.beta | character | “1;25” | Beta weights (a;b), multiple sets with commas |
--is_equal_weight_in_groupTest | logical | FALSE | Use equal weights |
--is_single_in_groupTest | logical | FALSE | Output single-variant results |
--is_output_markerList_in_groupTest | logical | FALSE | Output variant lists for each mask |
Conditional Analysis
| Parameter | Type | Default | Description |
--condition | character | ”” | Conditioning variants (chr:pos_ref/alt, comma-separated) |
--weights_for_condition | character | NULL | Weights for conditioning variants (; and , separated) |
Sparse GRM
| Parameter | Type | Default | Description |
--sparseGRMFile | character | ”” | Sparse GRM file from Step 1 |
--sparseGRMSampleIDFile | character | ”” | Sample IDs for sparse GRM |
--relatednessCutoff | numeric | 0 | Kinship threshold |
--is_sparseGRM | logical | FALSE | Use sparse GRM |
Output
| Parameter | Type | Default | Description |
--SAIGEOutputFile | character | ”” | Required. Output file path |
--markers_per_chunk | numeric | 10000 | Variants per chunk (single-variant tests) |
--groups_per_chunk | numeric | 100 | Groups per chunk (set-based tests) |
--markers_per_chunk_in_groupTest | numeric | 100 | Variants per chunk for covariance matrix |
--is_output_moreDetails | logical | FALSE | Output genotype counts |
--is_overwrite_output | logical | TRUE | Overwrite existing output |
Variance Ratio Categories
| Parameter | Type | Default | Description |
--cateVarRatioMinMACVecExclude | character | “10,20.5” | Lower MAC bounds (must match Step 1) |
--cateVarRatioMaxMACVecInclude | character | “20.5” | Upper MAC bounds (must match Step 1) |
Advanced Options
| Parameter | Type | Default | Description |
--is_fastTest | logical | FALSE | Use fast test mode |
--pval_cutoff_for_fastTest | numeric | 0.05 | P-value cutoff for fast mode |
--is_noadjCov | logical | TRUE | Regress covariates from genotypes |
--max_MAC_for_ER | numeric | 4 | Max MAC for efficient resampling |
--is_EmpSPA | logical | FALSE | Use empirical SPA |
step3_gene_pvalue_qtl.R
Calculates gene-level p-values using ACAT (Aggregated Cauchy Association Test).
| Parameter | Type | Default | Description |
--assocFile | character | ”” | Required. Association file from Step 2 |
--weightFile | character | ”” | Weight file (2 columns: MarkerID, weight) |
--geneName | character | ”” | Gene name for output (default: “gene”) |
--genePval_outputFile | character | ”” | Required. Output file path |
Note: Weight file format requires header with columns “MarkerID” and “weight”.
makeGroupFile.R
Creates group files for set-based association tests.
Choose one format:
VCF Files
| Parameter | Type | Default | Description |
--vcfFile | character | ”” | VCF file path |
--vcfFileIndex | character | ”” | VCF index (.csi) |
--vcfField | character | “DS” | Field: “DS” or “GT” |
SAV Files
| Parameter | Type | Default | Description |
--savFile | character | ”” | SAV file path |
--savFileIndex | character | ”” | SAV index (.s1r) |
BGEN Files
| Parameter | Type | Default | Description |
--bgenFile | character | ”” | BGEN file (v1.2, 8-bit) |
--bgenFileIndex | character | ”” | BGEN index (.bgi) |
--sampleFile | character | ”” | Sample file for BGEN |
PLINK Files
| Parameter | Type | Default | Description |
--bedFile | character | ”” | PLINK bed file |
--bimFile | character | ”” | PLINK bim file |
--famFile | character | ”” | PLINK fam file |
Region and Output
| Parameter | Type | Default | Description |
--regionFile | character | ”” | Required. Regions file (chr, start, end; no header) |
--AlleleOrder | character | “alt-first” | Allele order: “alt-first” or “ref-first” |
--outputPrefix | character | ”~/” | Required. Output path and prefix |
Required parameters are marked in bold in the Description column. These must be specified for the script to run.