Fig. 4: DHS components illuminate genetic associations and heritability.
From: Index and biological spectrum of human DNase I hypersensitive sites
a, Association of DHSs with GWAS traits by component, shown as enrichment ratios for increasingly stringent subsets of variants (canonical genome-wide significance threshold of 5 × 10−8 indicated). Grey, enrichments for top 15 component-associated biosamples. b, Stratified LD-score regression (S-LDSC) for traits shown in a associates GWAS variants and DHS components. Heritability enrichment for the top three most enriched baseline annotations (white); the full DHS index (grey); and trait-relevant DHS components (red). *Statistically significant enrichment (one-sided test, 1% FDR). c, Enrichment of DHS component (x-axis) heritability across 261 GWAS traits (y-axis). Greyscale indicates heritability enrichment levels for statistically significant associations (one-sided tests, 1% FDR). Right, sampling of labels of enriched traits for each component. Arrows, traits from a and b. d, Distribution of S-LDSC coefficient z-scores across 261 GWAS traits, shown for all baseline annotations (dashed grey line), top 15 DHS component-associated biosamples (solid grey line) and DHS components (black line). e, S-LDSC coefficient z-scores for selected traits (lupus, q = 0.002; maximum heart rate during fitness, q = 0.016; alcohol drinking status, q = 0.009), shown for all biosamples (grey lines), top 15 component-associated biosamples (coloured ticks) and DHS components (coloured arrows). f, Stronger heritability contribution of component-concordant DHSs shown by stratifying S-LDSC z-scores by DHS types. Boxes, medians and IQRs (25–75%); whiskers, 1.5 × IQRs; n = 261 GWAS traits. Grey areas in d–f indicate S-LDSC z-scores (S-LDSC coefficients, normalized using estimated standard errors) with P < 0.01; FDR-corrected q-values shown for traits in e.
