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. 2023 Jan 13;3(2):100248. doi: 10.1016/j.xgen.2022.100248

Figure 2.

Figure 2

Genetic variants and host defense traits targeted by positive selection

(A) Enrichments in missense, whole blood cis-eQTL, or ASB variants for variants with psel < 10−2 and psel < 10−4, across the genome (“All loci”) or within the 89 candidate positively selected loci (“89 loci”). Only variants of transcripts annotated as “protein coding” were considered for the analysis of variant annotations. Red and black circles indicate significant and non-significant enrichments, respectively, and error bars indicate the boundaries of the 95% CI for the estimated odds ratios. The three eQTL groups were defined on the basis of the statistical significance of the eQTL association, peQTL < 5 × 10−8, peQTL <10−15, or peQTL <10−50.

(B) Significant associations (p < 10−5; https://genetics.opentargets.org) in PheWAS between positively selected missense variants overlapping host defense genes and hematopoietic traits, infections, or inflammatory disorders.

(C) Enrichments in variants associated with the 36 hematopoietic traits studied for variants with psel <10−2, across the genome (“All loci”) or within the 89 candidate positively selected loci (“89 loci”). Red and black circles indicate significant and non-significant enrichments, respectively, and error bars indicate the boundaries of the 95% CI for the estimated odds ratios. Orange and gray triangles indicate significant and non-significant enrichments, respectively, after exclusion of the HLA locus.

(D) Left: mean polygenic score across four equally spaced epochs for each of the hematopoietic traits. Right: −log10(p value) for the significant increases or decreases in each hematopoietic trait over the last 10,000 years (dot), before (upward-pointing triangle) or after (downward-pointing triangle) the beginning of the Bronze Age. Light gray symbols represent non-significant trajectories. The inset shows the decrease in polygenic score over time for platelet counts, which has the highest −log10(p value). The black line is the regression line. (C and D) Traits followed by “_p” indicate the percentage of the cell type considered, whereas other traits are absolute counts.

See also Figure S5A.