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

Communications Biology

Dean Bok¹  Jane Hu¹  Boxiang Liu²  Douglas Vollrath³  Ming Chen³  Gillie Benchorin³  Nathan S. Abell³  Melissa A. Calton³  Stephen B. Montgomery⁴  Xin Li⁵  Brunilda Balliu⁵  Michael J. Gloudemans⁶ 

[1] 0000 0000 9632 6718, grid.19006.3e, Department of Ophthalmology, Jules Stein Eye Institute, UCLA, 90095, Los Angeles, CA, USA;0000000419368956, grid.168010.e, Department of Biology, Stanford University, 94305, Stanford, CA, USA;0000000419368956, grid.168010.e, Department of Genetics, Stanford University School of Medicine, 94305, Stanford, CA, USA;0000000419368956, grid.168010.e, Department of Genetics, Stanford University School of Medicine, 94305, Stanford, CA, USA;0000000419368956, grid.168010.e, Department of Pathology, Stanford University School of Medicine, 94305, Stanford, CA, USA;0000000419368956, grid.168010.e, Department of Pathology, Stanford University School of Medicine, 94305, Stanford, CA, USA;0000000419368956, grid.168010.e, Program in Biomedical Informatics, Stanford University School of Medicine, 94305, Stanford, CA, USA;

DOI  :  10.1038/s42003-019-0430-6

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY