Title: | Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma |
Author: |
... 60 more authors Show all authors |
Date: | 2024-01-09 |
Language: | English |
Scope: | 4869889 |
School: | Health Sciences |
Department: | Faculty of Medicine |
Series: | Nature Communications; 15(1) |
ISSN: | 2041-1723 |
DOI: | 10.1038/s41467-023-44380-y |
Subject: | Humans; Genome-Wide Association Study; Glaucoma, Open-Angle/genetics; Gene Expression Regulation; Causality; Glaucoma/genetics; General Chemistry; General Biochemistry,Genetics and Molecular Biology; General Physics and Astronomy |
URI: | https://hdl.handle.net/20.500.11815/4810 |
Citation:Hamel , A R , Yan , W , Rouhana , J M , Monovarfeshani , A , Jiang , X , Mehta , P A , Advani , J , Luo , Y , Liang , Q , Rajasundaram , S , Shrivastava , A , Duchinski , K , Mantena , S , Wang , J , van Zyl , T , Pasquale , L R , Swaroop , A , Gharahkhani , P , Khawaja , A P , MacGregor , S , Hewitt , A W , Schuster , A K , Viswanathan , A C , Lotery , A J , Cree , A J , Pang , C P , Brandl , C , Klaver , C C W , Hayward , C , Khor , C C , Cheng , C Y , Hammond , C J , van Duijn , C , Mackey , D A , Stefansson , E , Vithana , E N , Pasutto , F , Jonansson , F , Thorleifsson , G , Koh , J , Wilson , J F , Craig , J E , Vergroesen , J E , Fingert , J H , Jonas , J B , Stefánsson , K , Burdon , K P , Chen , L J , Kass , M , Jansonius , N M , Pfeiffer , N , Polašek , O , Foster , P J , Mitchell , P , Hysi , P G , Wojciechowski , R , Driessen , S J , Tompson , S W J , Young , T L , Wong , T Y , Aung , T , Thorsteinsdottir , U , de Vries , V A , Ramdas , W D , Wang , Y X , Chen , R , Vitart , V , Sanes , J R , Wiggs , J L & Segrè , A V 2024 , ' Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma ' , Nature Communications , vol. 15 , no. 1 , 396 , pp. 396 . https://doi.org/10.1038/s41467-023-44380-y
|
|
Abstract:Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.
|
|
Description:© 2024. The Author(s).
|