Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration
Summary: 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 a...
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doaj-1d550e817e174a2695fd2849cb2c47672020-11-25T00:53:33ZengElsevierCell Reports2211-12472020-01-0130412461259.e6Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular DegenerationLuz D. Orozco0Hsu-Hsin Chen1Christian Cox2Kenneth J. Katschke, Jr.3Rommel Arceo4Carmina Espiritu5Patrick Caplazi6Sarajane Saturnio Nghiem7Ying-Jiun Chen8Zora Modrusan9Amy Dressen10Leonard D. Goldstein11Christine Clarke12Tushar Bhangale13Brian Yaspan14Marion Jeanne15Michael J. Townsend16Menno van Lookeren Campagne17Jason A. Hackney18Department of Bioinformatics and Computational Biology, Genentech, South San Francisco, CA 94080, USADepartment of Biomarker Discovery OMNI, Genentech, South San Francisco, CA 94080, USADepartment of Immunology Discovery, Genentech, South San Francisco, CA 94080, USADepartment of Immunology Discovery, Genentech, South San Francisco, CA 94080, USADepartment of Pathology, Genentech, South San Francisco, CA 94080, USADepartment of Pathology, Genentech, South San Francisco, CA 94080, USADepartment of Pathology, Genentech, South San Francisco, CA 94080, USADepartment of Pathology, Genentech, South San Francisco, CA 94080, USADepartment of Molecular Biology, Genentech, South San Francisco, CA 94080, USADepartment of Molecular Biology, Genentech, South San Francisco, CA 94080, USADepartment of Human Genetics, Genentech, South San Francisco, CA 94080, USADepartment of Bioinformatics and Computational Biology, Genentech, South San Francisco, CA 94080, USA; Department of Molecular Biology, Genentech, South San Francisco, CA 94080, USADepartment of Bioinformatics and Computational Biology, Genentech, South San Francisco, CA 94080, USADepartment of Human Genetics, Genentech, South San Francisco, CA 94080, USADepartment of Human Genetics, Genentech, South San Francisco, CA 94080, USADepartment of Immunology Discovery, Genentech, South San Francisco, CA 94080, USADepartment of Biomarker Discovery OMNI, Genentech, South San Francisco, CA 94080, USA; Corresponding authorDepartment of Immunology Discovery, Genentech, South San Francisco, CA 94080, USA; Corresponding authorDepartment of Bioinformatics and Computational Biology, Genentech, South San Francisco, CA 94080, USA; Corresponding authorSummary: 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. : To find genes underlying risk for age-related macular degeneration, Orozco et al. analyze human ocular transcriptomes in conjunction with genotypes and build a single-nucleus atlas. They identify 15 putative causal genes, of which TSPAN10 and TRPM1 were enriched in retinal pigment epithelium, the site of early disease pathology. Keywords: eQTL, NucSeq, single cell, RNA-seq, age-related macular degeneration, AMD, retinal pigment epithelium, retina, GWAShttp://www.sciencedirect.com/science/article/pii/S2211124719317474 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luz D. Orozco Hsu-Hsin Chen Christian Cox Kenneth J. Katschke, Jr. Rommel Arceo Carmina Espiritu Patrick Caplazi Sarajane Saturnio Nghiem Ying-Jiun Chen Zora Modrusan Amy Dressen Leonard D. Goldstein Christine Clarke Tushar Bhangale Brian Yaspan Marion Jeanne Michael J. Townsend Menno van Lookeren Campagne Jason A. Hackney |
spellingShingle |
Luz D. Orozco Hsu-Hsin Chen Christian Cox Kenneth J. Katschke, Jr. Rommel Arceo Carmina Espiritu Patrick Caplazi Sarajane Saturnio Nghiem Ying-Jiun Chen Zora Modrusan Amy Dressen Leonard D. Goldstein Christine Clarke Tushar Bhangale Brian Yaspan Marion Jeanne Michael J. Townsend Menno van Lookeren Campagne Jason A. Hackney Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration Cell Reports |
author_facet |
Luz D. Orozco Hsu-Hsin Chen Christian Cox Kenneth J. Katschke, Jr. Rommel Arceo Carmina Espiritu Patrick Caplazi Sarajane Saturnio Nghiem Ying-Jiun Chen Zora Modrusan Amy Dressen Leonard D. Goldstein Christine Clarke Tushar Bhangale Brian Yaspan Marion Jeanne Michael J. Townsend Menno van Lookeren Campagne Jason A. Hackney |
author_sort |
Luz D. Orozco |
title |
Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration |
title_short |
Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration |
title_full |
Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration |
title_fullStr |
Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration |
title_full_unstemmed |
Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration |
title_sort |
integration of eqtl and a single-cell atlas in the human eye identifies causal genes for age-related macular degeneration |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2020-01-01 |
description |
Summary: 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. : To find genes underlying risk for age-related macular degeneration, Orozco et al. analyze human ocular transcriptomes in conjunction with genotypes and build a single-nucleus atlas. They identify 15 putative causal genes, of which TSPAN10 and TRPM1 were enriched in retinal pigment epithelium, the site of early disease pathology. Keywords: eQTL, NucSeq, single cell, RNA-seq, age-related macular degeneration, AMD, retinal pigment epithelium, retina, GWAS |
url |
http://www.sciencedirect.com/science/article/pii/S2211124719317474 |
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