Extended Data Fig. 2: Classification of ancestry-associated differences.

(A) Correlation of population differentially expressed (popDE) effects calculated with global or local ancestry effects (Pearson’s correlation coefficient reported). (B) Distribution depicting the relationship between popDE genes and popDE epigenetic changes across both conditions. Genes more highly expressed in individuals with high proportions of European ancestry (fold change < -0.5, FDR < 0.10) are nearby popDE epigenetic regions (FDR < .10) that show increased levels of chromatin accessibility, H3K27ac, H3K4me1 and H3K4me3 in individuals with increased European ancestry levels. Black lines represent means. (C) Distributions of individual mean scores of inflammatory pathways in the flu-infected condition comparable to Fig. 2c which shows non-infected condition distributions. A higher score indicates a strong expression of genes or epigenetic marks nearby genes within the Hallmark inflammatory response pathway. (D) Individual mean score differences between the population-groups for the Hallmark “inflammatory pathway” in the non-infected and (C) flu-infected conditions remain consistent when reducing popDE effects FDR from 10% to 5%. P values in panels C and D calculated using a two-sided Wilcoxon rank sum test. (E) Population-group differences utilizing popDR effects to calculate individual transcriptional response score across 6 immune pathways remain consistent with varying FDR thresholds (20%, 10% and 5%). (n = 35 individuals: 14 AF, 21 EU) P values calculated using a two-sided Wilcoxon rank sum test. The maxima and minima are the upper and lower points, respectively. The center line represents the median, and the top and bottom lines are the 75% and 25% percentile, respectively. (F) The distribution of Spearman’s correlation between the predicted and observed mean scores for the various pathways using different alphas.