Fig. 2
Association analyses reveal Cacna2d1 as a candidate for IOP modulation. a IOP levels vary among the BXD strains. IOP of BXD strains carrying wild-type alleles of Tyrp1 and Gpnmb (WT/WT; blue bars), wild-type Tyrp1 and mutant Gpnmb (WT/MUT; green bars), mutant Tyrp1 and WT Gpnmb (MUT/WT; yellow bars), and mutant alleles of both genes (MUT/MUT; red bars) are shown. n = 65 strains, age = 9.1–13 months. Values denote IOP levels on mmHg scale (mean ± SEM). b No differences in IOP between sexes. There is a strong statistical association between the IOP of males and females (P < 0.0001). The relationship between the sexes is positively correlated (R 2 = 0.37, Pearson correlation coefficient = 0.62). c Genetic interval mapping revealed a single significant eQTL on proximal Chr 5. This is distinct from the locations of Tyrp1 and Gpnmb in the genome (black vertical lines on Chr 4 and Chr 6, respectively). d Tyrp1 and Gpnmb haplotypes do not influence IOP in BXD mice. The scatter plot shows average IOP of BXD strains carrying wild-type alleles of Tyrp1 and Gpnmb (WT/WT), wild-type allele of Tyrp1 and mutant allele of Gpnmb (MUT/WT), mutant allele of Tyrp1 and wild-type allele of Gpnmb (WT/MUT), and mutant alleles of both genes (MUT/MUT) (n = 65, P = 0.13, age = 9.1–13 months). P-value was calculated using an ANOVA. e Stringent selection criteria for selecting candidate genes. f A significant QTL for IOP is present on chromosome 5 between 14–19 Mb. Cacna2d1 is the strongest candidate gene located in the peak QTL. g Gene set enrichment analysis for positive correlates of Cacna2d1. Gene correlates of Cacna2d1 were significantly enriched for localization to the plasma membrane. False discovery rate (FDR) cutoff was set as q ≤ 0.25. h Gene set enrichment analysis of genes positively correlated with Cacna2d1 presented as molecular function groupings. Categories that are statistically over-represented are shown with their normalized enrichment score (NES) listed next to the bars
