Eye Multiome

Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Genome-wide association studies (GWASs) of AMD have identified dozens of risk loci that may house disease targets. However, variants at these loci are largely noncoding, making it difficult to assess their function and whether they are causal. Here, we present a single-cell gene expression and chromatin accessibility atlas of human retinal pigment epithelium (RPE) and choroid to systematically analyze both coding and noncoding variants implicated in AMD. We employ HiChIP and activity-by-contact modeling to map enhancers in these tissues and predict cell and gene targets of risk variants. We further perform allele-specific self-transcribing active regulatory region sequencing (STARR-seq) to functionally test variant activity in RPE cells, including in the context of complement activation. Our work nominates pathogenic variants and mechanisms in AMD and offers a rich and accessible resource for studying diseases of the RPE and choroid.

Explore

Cell-type gene expression browser	Single Cell Portal UMAP	Chromatin accessibility tracks, HiChIP loops, and Activity-by-Contact connections

Data

Raw and processed scRNA-seq, scATAC-seq, and HiChIP files: GSE262151
Raw and processed STARR-seq files: GSE289703
Deep learning (ChromBPNet) models: https://doi.org/10.5281/zenodo.14031498
scRNA-seq/scATAC-seq code: https://github.com/seankwang/RPEchoroid-multiome

Citation

If you use this resource in your research, please cite:

Sean K. Wang,* Jiaying Li,* Surag Nair, Reshma Kosaraju, Yun Chen, Yuanyuan Zhang, Anshul Kundaje, Yuwen Liu, Ningli Wang, Howard Y. Chang. Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration. Cell Reports (2026). DOI: 10.1016/j.celrep.2025.116814. * Equal contribution.