Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate pathogenic variants in age-related macular degeneration
机构：[1]Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.[2]Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA.[3]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.首都医科大学附属北京同仁医院首都医科大学附属同仁医院[4]Department of Computer Science, Stanford University, Stanford, CA, USA.[5]Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.[6]Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.[7]Kunpeng Institute of Modern Agriculture at Foshan, Chinese Academy of Agricultural Sciences, Foshan, China.[8]Henan Academy of Innovations in Medical Science, Henan, China.[9]Current address: Amgen Research, South San Francisco, CA, USA.
Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Genome-wide association studies (GWAS) 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 new pathogenic variants and mechanisms in AMD and offers a rich and accessible resource for studying diseases of the RPE and choroid.
基金：
This work was supported
by National Institutes of Health (NIH) grant RM1-HG007735 (to H.Y.C.). S.K.W. was supported
by a National Eye Institute training grant (T32EY027816) and the Knights Templar Eye
Foundation. H.Y.C. was an Investigator of the Howard Hughes Medical Institute.
语种：
外文
PubmedID：
第一作者：
第一作者机构：[1]Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.[2]Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA.
共同第一作者：
通讯作者：
通讯机构：[1]Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.[3]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.[5]Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.[6]Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.[7]Kunpeng Institute of Modern Agriculture at Foshan, Chinese Academy of Agricultural Sciences, Foshan, China.[8]Henan Academy of Innovations in Medical Science, Henan, China.[9]Current address: Amgen Research, South San Francisco, CA, USA.
推荐引用方式(GB/T 7714)：
Wang Sean K,Li Jiaying,Nair Surag,et al.Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate pathogenic variants in age-related macular degeneration[J].Biorxiv : The Preprint Server For Biology.2025,doi:10.1101/2025.03.21.644670.
APA：
Wang Sean K,Li Jiaying,Nair Surag,Korasaju Reshma,Chen Yun...&Chang Howard Y.(2025).Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate pathogenic variants in age-related macular degeneration.Biorxiv : The Preprint Server For Biology,,
MLA：
Wang Sean K,et al."Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate pathogenic variants in age-related macular degeneration".Biorxiv : The Preprint Server For Biology .(2025)
