|
Fig. 3 Collapsing analysis identifies KDELR3 as an EM gene. a Manhattan plots of the gene-based collapsing analysis. An excess of rare PTVs in EM cases within genes were tested using Fisher’s exact test [FET], Red line, P = 0.05/6335 = 7.89 × 10−06. b The top ten genes from collapsing analyses under the same model are shown, including the exact numbers of all qualifying cases and controls and statistical calculations of association (OR and FET P). c Linear schematic of the KDELR3 and VN1R4 encoded protein and location of genetic variants identified by WES. Frameshift variants are in red, Nonsense variants in orange. d Multiple sequence alignment indicating a degree of sequence conservation across species at the locations of KDELR3 and VN1R4 rare PTVs. e Cumulative distribution of SER in MAGIC cohort. The x-axis is the SER of right (OD) and left (OS) eyes. The y-axis is the cumulative fraction of individuals. red: individuals carrying KDELR3 PTVs, black: individuals without carrying KDELR3 PTVs. f Violin plots indicate the expression of KDELR3 genes retina and other tissues in GTEx. Sample size for each tissue is shown in parentheses. The center line in the box plots contained within each violin plot shows the median, the box edges depict the interquartile range (IQR), and whiskers mark 1.5× the IQR. The violin plot edges represent the minima and maxima values. g UMAP of all tissues single-cell data with cell colored based on the expression of KDELR3 genes for particular cell types. Gene expression levels are indicated by shades of red. SC Schwann cells, BCE B-cell, TCE T-cell, CM melanocytes, FB fibroblast, RPE retinal pigment epithelium, SMC smooth muscle cells, PER pericytes, RBC rod bipolar cells, ROD rods, mo macrophage, A artery, CC choriocapillaris, V vein, MOC monocytes, RBN retinal bipolar neuron, MEC melanocytes, MAC macrophage, ATC active T cells, CEC corneal epithelial cells.