Paired DNA and RNA sequencing uncovers common and rare variation regulating human retinal gene expression.

Genetic disorders impacting vision affect millions of individuals worldwide, including age-related macular degeneration (common) and inherited retinal disorders (rare). There is an incomplete understanding of the impact of genetic variation on gene expression in the human retina and its role in genetic disorders. Through the generation of whole genome sequencing and bulk RNA-sequencing of neurosensory retina and retinal pigment epithelium from 201 post-mortem eyes, we uncover common and rare genomic variants shaping retinal expression profiles. This includes 1,483,595 significant cis-expression quantitative trait loci impacting 9,959 and 3,699 genes in neurosensory retina and retinal pigment epithelium, respectively, with associated genomic variants enriched to cis-candidate regulatory elements and notable shared eGenes between both tissues. We also detect 1051 expression outliers and prioritise 299 rare non-coding single-nucleotide, structural variants or copy number variants as plausible drivers for 28% of outlier events. This study increases understanding of gene expression regulation in the human retina.