Summary Statistics Pipeline

Summary Statistics Pipeline

Traditional Knockoff requires individual-level genotype data, but GWAS typically only release summary statistics (Z-scores, p-values, etc.). This pipeline uses GhostKnockoff and LAVA-Knock to perform Knockoff analyses based solely on summary statistics:

• GhostKnockoff: Reconstructs knockoff statistics from summary data using LD structure from a reference panel.
• LAVA-Knock: Extends to local genetic correlation analyses and supports joint multi-trait analysis.
• No individual data required: Runs with only Z-scores and a reference panel (e.g., 1000 Genomes).

Main Features

• Variable selection (--mode select): GhostKnockoff + LAVAKnock FDR control, outputs significant variants.
• Local genetic correlation (--mode correl): LAVA-Knock bivariate window analysis, outputs window-level local correlations and knockoff-filtered results.

Pipeline Versions: Standard vs Fast

If the Python environment cannot be loaded, the pipeline will automatically fall back to the standard implementation.

Quick Start

The following commands can be run from the repository root. The default reference panel is the 1000 Genomes g1000_eur. Users may provide their own panel or genotype data. Provide a zscore file zscore.txt, and the pipeline will chunk based on the specified genome coordinate system GRCh37 or GRCh38.

1) Install dependencies

Rscript install_packages.R

2) Variable selection (reference panel)

Rscript run_pipeline.R --mode select \
  --zscore zscore.txt \
  --panel g1000_eur \
  --ld_coord GRCh37 \
  --py_accel -v -o results

• Automatically parses chr:pos:ref:alt or CHR/POS columns in zscore.txt, matching to the reference panel by CHR+POS.
• --panel can be omitted (default g1000_eur/g1000_eur).
• --ld_coord must explicitly specify LD block coordinates (GRCh37 or GRCh38).

3) Variable selection (real genotypes)

Rscript run_pipeline.R --mode select \
  --zscore zscore.txt \
  --geno_plink genotype \
  --ld_coord GRCh37 \
  -o results -v

4) Local genetic correlation (example)

Rscript run_pipeline.R --mode correl \
  --zscore zscore.txt \
  --panel g1000_eur/g1000_eur \
  --py_accel -v -o results

To scale to the whole genome, iterate over chromosomes 1–22 (or generate specific windows using scripts/build_info_from_plink.R).

Input Formats and Auto-detection

• Variant info: CSV with columns rsid, chr, pos_bp. Can be generated from a PLINK panel using scripts/build_info_from_plink.R.
• GWAS summary:
  • Standard: CHR, POS, Z.
  • rsid + value only: automatically converted via normalize_gwas_table(); use scripts/convert_zscore_to_gwas.R for batch preprocessing.
  • Multi-trait: --multi_gwas <file> --zcols col1,col2.
• Genotypes / reference panel:
  • --geno_rds: RDS matrix (column names rsid or chr:pos).
  • --geno_csv: CSV with --geno_format samples_by_snps|snps_by_samples.
  • --geno_plink: PLINK prefix, read via snpStats::read.plink.
  • If real genotypes are not provided, --ref_plink is used automatically (default g1000_eur/g1000_eur).

Output Description

Selection mode

Output file: results/selection/<info>_<pheno>_selection.csv

Columns include:

• id, rsid, chr, pos
• pval.orginal, pval.knockoff*
• W, Qvalue, selected
• geno_source

If chunking by LD blocks (--ld_coord), an additional <prefix>_chunk_summary.csv is produced, recording for each chunk:

• range
• source (ld_block/fallback)
• number selected

Correlation mode

Output files:

• results/correlation/<info>_<pheno1>__<pheno2>_bivariate.csv
• results/correlation/<info>_<pheno1>__<pheno2>_significant_windows.csv

Directory Overview

g1000_eur/                    # default reference panel (.bed/.bim/.fam/.synonyms)
demo_chr10_10_20Mb.*          # example real genotypes (PLINK)
info_chr10_10_20Mb.csv        # example Info extracted from reference panel
zscore_chr10_10_20Mb.tsv      # example GWAS subset
zscore_formatted.tsv          # converted standard format
results/                      # analysis outputs
  ├── selection/              # variable selection results
  └── correlation/            # local genetic correlation results