Bioresearch Ld Reference Management

BioResearch Agent — LD Reference Panel Management Skill

Capability

Manages ancestry-specific LD reference panels and performs LD-based instrument clumping:

1. Ancestry-aware LD simulation — generates realistic LD block structures for 5 super-populations (AFR / EUR / EAS / SAS / AMR) with biologically grounded parameters: AFR has shortest LD blocks (older population, more recombination), non-AFR populations have longer blocks (serial founder effects). Block lengths and LD decay rates follow 1000 Genomes empirical patterns.
2. Greedy LD clumping — PLINK --clump-style algorithm: sort SNPs by p-value, greedily select lead SNPs, remove proxies within a distance + r² threshold. Returns independent instrument set.
3. LD score computation — per-SNP LD scores (sum of r² with neighbors) for stratified LDSC heritability partitioning across ancestries.
4. Cross-ancestry LD comparison — pairwise LD decay curves and block-length distributions, quantifying how LD structure differs across populations (the root cause of ancestry-portability failure in MR).

Returns a clumped instrument set + LD score table + ancestry comparison report, not a causal claim.

Run

bioresearch run ld-reference-management --ancestry EUR --n-snps 500 --seed 42 --output-dir outputs/ld-reference

Outputs (in --output-dir)

• ld_clumped_instruments.csv — independent lead SNPs after clumping (SNP, CHR, POS, P, cluster_id)
• ld_scores.csv — per-SNP LD scores per ancestry (SNP, ancestry, ld_score)
• ld_decay_comparison.csv — pairwise LD decay curves (distance, mean_r2, ancestry_pair)
• ld_block_summary.csv — per-ancestry block-length statistics (mean, median, max, n_blocks)
• ld_ancestry_heatmap.png — LD decay heatmap across ancestries
• ld_evidence_package.json — reproducible Evidence Package (provenance + parameters + grade)

Note

This skill dispatches to the framework's ld-reference-management workflow / demo_ld_reference.py. It adds no analysis of its own; all computations run in the workflow modules. By default uses simulated LD panels with ancestry-specific parameters to validate the clumping pipeline — real-data deployment would use PLINK 2.0 with 1000 Genomes Phase 3 reference panels per ancestry. Evidence grade is C (methodology validation). Part of Phase 3a (cross-ancestry MR, CPU-only).