Fig. 3: Neanderthal alleles confer directional effects for some traits.

For eight traits with heritability enrichment in Altai-matching introgressed variants (Fig. 1D), we assessed the direction of effect of the Neanderthal alleles with two approaches. The first intersects introgressed Altai-matching Neanderthal alleles (LD-expanded to r² = 1) with strongly associated (P < 1 × 10⁻⁸) variants from each GWAS. A For each trait, we plot the number of variants by the direction of effect of the Neanderthal allele. Variants in perfect LD (r² = 1) are pruned. Four traits show a significant difference (q < 0.05, one-tailed χ2 goodness of fit test) in the direction of effect: increased balding, younger menopause age, increased forced vital capacity, and morning person. For example, of the 17 Neanderthal alleles associated with balding, 15 are associated with hair loss and only two with full hair. Sunburn, Heel T score, and WBC count also show modest biases. B This second approach, SLDP regression, considers the direction of effect over all variants (n = 1,187,349), not just those with the largest effects. For each variant, we compute the marginal correlation (α̂) of the variant to the trait versus the Neanderthal LD profile (Rν). For the sunburn trait, we observe a positive correlation indicating a significant uni-directional relationship genome-wide between Neanderthal introgressed alleles and risk for sunburn (empirical null distribution P = 0.001, q = 0.02). For visualization, we bin Rν into 10 equally spaced intervals and plot the average α̂ with 95% bootstrapped confidence intervals.