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  1. Article ; Online: QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.

    Advani, Jayshree / Mehta, Puja A / Hamel, Andrew R / Mehrotra, Sudeep / Kiel, Christina / Strunz, Tobias / Corso-Díaz, Ximena / Kwicklis, Madeline / van Asten, Freekje / Ratnapriya, Rinki / Chew, Emily Y / Hernandez, Dena G / Montezuma, Sandra R / Ferrington, Deborah A / Weber, Bernhard H F / Segrè, Ayellet V / Swaroop, Anand

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1972

    Abstract: DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering ... ...

    Abstract DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype-environment interaction in retina.
    MeSH term(s) Humans ; DNA Methylation/genetics ; Epigenesis, Genetic ; Epigenome ; Macular Degeneration/genetics ; Retina
    Language English
    Publishing date 2024-03-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46063-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma.

    Hamel, Andrew R / Yan, Wenjun / Rouhana, John M / Monovarfeshani, Aboozar / Jiang, Xinyi / Mehta, Puja A / Advani, Jayshree / Luo, Yuyang / Liang, Qingnan / Rajasundaram, Skanda / Shrivastava, Arushi / Duchinski, Katherine / Mantena, Sreekar / Wang, Jiali / van Zyl, Tavé / Pasquale, Louis R / Swaroop, Anand / Gharahkhani, Puya / Khawaja, Anthony P /
    MacGregor, Stuart / Chen, Rui / Vitart, Veronique / Sanes, Joshua R / Wiggs, Janey L / Segrè, Ayellet V

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 396

    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 ... ...

    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.
    MeSH term(s) Humans ; Genome-Wide Association Study ; Glaucoma, Open-Angle/genetics ; Gene Expression Regulation ; Causality ; Glaucoma/genetics
    Language English
    Publishing date 2024-01-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-44380-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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