LRCQ: phenome-wide heritability enrichment of genomic loci from GWAS summary statistics

LRCQ estimates clump-level phenome-wide heritability enrichment from 30+ GWAS, finding 70 omni-loci (99 LD clumps) at FDR 5% in 444 Pan-UK Biobank European-ancestry studies.

• Why it matters: GWAS pleiotropy signals are confounded by linkage disequilibrium and shared study confounding, and existing pleiotropy metrics cannot separate these sources across many traits.
• What they did: LRCQ regresses squared Z-scores from many GWAS jointly on squared LD, using per-trait LDSC intercepts and heritabilities fitted earlier, with standard errors that account for sample overlap and genetic correlation.
• The result: In simulations it was unbiased for the clump-level estimand, and in UK Biobank it showed strongly non-uniform enrichment (SD 8.3 vs genome mean 1), enabling an LD-corrected map of phenome-wide genetic variance.

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