Evidence map›Paper›PMID 41528844›Full record

ArticleCell reports2026

Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration.

Sean K Wang, Jiaying Li, Surag Nair, Reshma Kosaraju, Yun Chen, Yuanyuan Zhang, Anshul Kundaje, Yuwen Liu, Ningli Wang, Howard Y Chang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Genetic evidence and cross-species functional characterization implicateProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. An Integrated Multi-omics Single Cell Atlas of the Human RPE and Choroid.bioRxiv : the preprint server for biology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Sean K WangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA; Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA.
Jiaying LiDepartment of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA; Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Surag NairDepartment of Computer Science, Stanford University, Stanford, CA, USA.
Reshma KosarajuCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Yun ChenState Key Laboratory of Genome and Multi-omics Technologies, Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
Yuanyuan ZhangState Key Laboratory of Genome and Multi-omics Technologies, Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
Anshul KundajeDepartment of Computer Science, Stanford University, Stanford, CA, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Yuwen LiuState Key Laboratory of Genome and Multi-omics Technologies, Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China; Kunpeng Institute of Modern Agriculture at Foshan, Chinese Academy of Agricultural Sciences, Foshan, China. Electronic address: liuyuwen@caas.cn.
Ningli WangBeijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Henan Academy of Innovations in Medical Science, Zhengzhou, China. Electronic address: wningli@vip.163.com.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: howchang@stanford.edu.

Funding

Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
NHGRI NIH HHS RM1 HG007735
6 · The paper itself

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.

Indexed as

ChoroidEnhancer Elements, GeneticMacular DegenerationRetinal Pigment EpitheliumSingle-Cell AnalysisGenome-Wide Association StudyHumansMultiomicsSingle-Cell Gene Expression Analysisage-related macular degenerationchoroidCP: genomicsepigenomicsHiChIPmulti-omicsretinal pigment epitheliumsingle-cell ATAC-seqsingle-cell RNA-seqSTARR-seq

Identifiers

PMID41528844
PMCPMC12971065

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.