Fig. 1: Complex trait heritability is broadly depleted in regions with Neanderthal ancestry and in introgressed variants.

A We focus on variants in regions of the human genome with remaining Neanderthal ancestry (red box). These variants (vertical lines and diamonds) have multiple evolutionary histories: most are segregating on nonintrogressed haplotypes (black), many are present in Eurasians due to introgression (red), and some of these introgressed alleles were shared among multiple Neanderthal populations including both the Altai Neanderthal and the introgressing Neanderthal population (diamonds). B Regions of the genome where Neanderthal ancestry remains (all variants in the red box in A) are depleted for heritability of 41 diverse complex traits (mean: 1.10 fold-depleted, two-tailed one-sample t-test P = 8 × 10⁻⁷) except for sunburn, skin color, and tanning. Each dot represents the heritability enrichment or depletion for a single trait estimated by stratified LD score regression (S-LDSC). Removing introgressed variants (red lines and diamonds in A, LD expanded to r² > 0.5), these regions are still broadly depleted for trait heritability (mean: 1.06 fold-depleted, two-tailed one-sample t-test P = 0.003). The boxplot centers represent medians, the boxes are bounded by the first and third quartiles, and the Tukey-style whiskers extend to a maximum of 1.5 × IQR beyond the box. C Introgressed variants (red lines and diamonds in A) contribute varying levels of heritability to different 41 traits. Most (76%) traits trend toward heritability depletion in introgressed variants (one-tailed binomial test P = 0.007). Bars for individual traits represent heritability enrichment estimates with 95% confidence intervals, which are calculated by S-LDSC standard errors using a block jackknife (n = 200). Traits are colored by their domain (legend); marked domains appear in later figures. These colors will be used in all figures. D Altai-matching introgressed variants (y-axis, diamonds in A) are more enriched for heritability than all introgressed variants (x-axis) for 78% of traits (one-tailed binomial test P = 0.0002, 1.02x vs. 0.78x). Traits with depletion below 0.125 are plotted on the baseline. These patterns are consistent when considering the Vindija Neanderthal (Fig. S3).