Genetic analyses of human fetal retinal pigment epithelium gene expression suggest ocular disease mechanisms

The retinal pigment epithelium (RPE) serves vital roles in ocular development and retinal homeostasis but has limited representation in large-scale functional genomics datasets. Understanding how common human genetic variants affect RPE gene expression could elucidate the sources of phenotypic varia...

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Bibliographic Details
Published in:Communications biology Vol. 2; no. 1; p. 186
Main Authors: Liu, Boxiang, Calton, Melissa A., Abell, Nathan S., Benchorin, Gillie, Gloudemans, Michael J., Chen, Ming, Hu, Jane, Li, Xin, Balliu, Brunilda, Bok, Dean, Montgomery, Stephen B., Vollrath, Douglas
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 20.05.2019
Nature Publishing Group
Subjects:
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Age
Alcohol Oxidoreductases - genetics
Biomedical and Life Sciences
Cells, Cultured
Chromosome Mapping
Energy Metabolism
Epithelium
Eye disorders
Fetus - cytology
Fetus - metabolism
Fetuses
Gene Expression
Genetic analysis
Genetic diversity
Genetic variability
Genetic Variation
Genome-wide association studies
Genome-Wide Association Study
Genomics
Homeostasis
Humans
Life Sciences
Macular degeneration
Macular Degeneration - genetics
Metabolism
Myopia
Myopia - genetics
Nonsense Mediated mRNA Decay
Quantitative Trait Loci
Retina
Retinal pigment epithelium
Retinal Pigment Epithelium - cytology
Retinal Pigment Epithelium - embryology
Retinal Pigment Epithelium - metabolism
Risk Factors
Transcriptome
Macular degeneration
Gene expression
Computational biology and bioinformatics
ISSN:2399-3642, 2399-3642
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Summary:The retinal pigment epithelium (RPE) serves vital roles in ocular development and retinal homeostasis but has limited representation in large-scale functional genomics datasets. Understanding how common human genetic variants affect RPE gene expression could elucidate the sources of phenotypic variability in selected monogenic ocular diseases and pinpoint causal genes at genome-wide association study (GWAS) loci. We interrogated the genetics of gene expression of cultured human fetal RPE (fRPE) cells under two metabolic conditions and discovered hundreds of shared or condition-specific expression or splice quantitative trait loci (e/sQTLs). Co-localizations of fRPE e/sQTLs with age-related macular degeneration (AMD) and myopia GWAS data suggest new candidate genes, and mechanisms by which a common RDH5 allele contributes to both increased AMD risk and decreased myopia risk. Our study highlights the unique transcriptomic characteristics of fRPE and provides a resource to connect e/sQTLs in a critical ocular cell type to monogenic and complex eye disorders. Boxiang Liu, Melissa Calton et al. report expression and splice quantitative trait locus analyses for human fetal retinal epithelium (fRPE) cells under two metabolic conditions. They identify loci linked to inherited ocular diseases and new candidate genes for age-related macular degeneration and myopia.
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ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-019-0430-6