Figure 2: Genetic influences on gene expression in human milk.

A) Counts of genes that have milk-specific eQTLs (orange, genes that have an eQTL only in milk or where the milk eQTL did not colocalize with any GTEx tissue, see Methods) vs. tissue-shared eQTLs (blue, genes with milk eQTLs that colocalized with at least one other tissue in GTEx). B) Fraction of genes in each category that overlapped with a milk trait QTL in the dairy cattle genome. C) Distributions of sequence-level constraint, measured by the loss-of-function observed/expected upper bound fraction (LOEUF) statistic³³. D) Enriched gene ontologies for genes with milk-specific (orange) or tissue-shared (blue) eQTLs. The dashed vertical line denotes a q-value of 10%. E) Sharing of eQTLs between milk and a subset of GTEx tissues, measured through statistical colocalization. Each bar shows each tissue’s similarity to milk, measured by the residual fraction of eQTLs colocalized with milk, after regressing out tissue sample size. Error bars represent a 95% confidence interval. F) LocusZoom genetic associations in the LMX1B region with milk gene expression (top panel) and breast cancer risk (bottom panel). Each data point represents a SNP, plotted by their chromosomal location (x-axis) and significance of association (y-axis), with colors corresponding to LD (linkage disequilibrium, r²) to the lead SNP for each dataset, shown as a purple diamond. G) Each point is a variant, plotted by the strength of association with milk gene expression (y-axis) and breast cancer risk (x-axis). Colors are the same as the top panel in 2F, with a purple diamond representing the lead milk eQTL SNP. The pattern of variants in the top right suggests a shared underlying causal variant.