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. 2020 Jan 28;30(4):1246-1259.e6.
doi: 10.1016/j.celrep.2019.12.082.

Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration

Luz D Orozco  1 , Hsu-Hsin Chen  2 , Christian Cox  3 , Kenneth J Katschke Jr  3 , Rommel Arceo  4 , Carmina Espiritu  4 , Patrick Caplazi  4 , Sarajane Saturnio Nghiem  4 , Ying-Jiun Chen  5 , Zora Modrusan  5 , Amy Dressen  6 , Leonard D Goldstein  7 , Christine Clarke  1 , Tushar Bhangale  6 , Brian Yaspan  6 , Marion Jeanne  3 , Michael J Townsend  8 , Menno van Lookeren Campagne  9 , Jason A Hackney  10
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Free article

Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration

Luz D Orozco et al. Cell Rep. .
Free article

Erratum in

Abstract

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.

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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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