Age-related macular degeneration (AMD) is a leading cause of vision loss. To better understand disease pathogenesis and identify causal genes in GWAS loci for AMD risk, we present a comprehensive database of human retina and retinal pigment epithelium (RPE). Our database comprises macular and non-macular RNA sequencing (RNA-seq) profiles from 129 donors, a genome-wide expression quantitative trait loci (eQTL) dataset that includes macula-specific retina and RPE/choroid, and single-nucleus RNA-seq (NucSeq) from human retina and RPE with subtype resolution from more than 100,000 cells. Using NucSeq, we find enriched expression of AMD candidate genes in RPE cells. We identify 15 putative causal genes for AMD on the basis of co-localization of genetic association signals for AMD risk and eye eQTL, including the genes TSPAN10 and TRPM1. These results demonstrate the value of our human eye database for elucidating genetic pathways and potential therapeutic targets for ocular diseases.
Keywords: AMD; GWAS; NucSeq; RNA-seq; age-related macular degeneration; eQTL; retina; retinal pigment epithelium; single cell.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Interests L.D.O., H.-H.C., C. Cox, K.J.K., R.A., C.E., P.C., S.S.N., Y.-J.C., Z.M., A.D., L.D.G., C. Clarke, T.B., B.Y., M.J., M.J.T., M.v.L.C., and J.A.H. were employees of Genentech at the time these studies were carried out.
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