Figure 2 |. Rare variant gene-level HbA1C associations show enrichment for genes involved in glycemic control and erythrocytic pathways in mice.
a, Boxplots displaying the percentile of gene-level P-values (relative to matched genes; grey) for genes thought to impact erythrocyte pathways (blue) and glycemic control (green) in mice. The horizontal dotted line at the 50th percentile indicates the expected median percentile under the null distribution. We used a one-sided Wilcoxon rank sum test to assess significant deviation of percentiles from matched genes; Wilcoxon P-values are displayed for each gene set. The numbers of genes in each gene set are indicated in the Supplementary Note. b, The fraction of genes with a negative effect on HbA1C levels among those (i) with HbA1C gene-level P ≤ 0.05 and (ii) within a significantly enriched (P ≤ 0.05) erythrocytic (n = 4) or glycemic (n = 5) gene set. The bars represent the fractions of genes observed across all gene sets, while the dots represent the fractions of genes observed for each individual gene set. We used a binomial test to assess deviation from the expected fraction of 50%. In a, the box plot indicates minimum, lower quartile, median, upper quartile, and maximum. In b, the error bars indicate standard error.