Advani, Jayshree and Mehta, Puja A. and Hamel, Andrew R. and Mehrotra, Sudeep and Kiel, Christina and Strunz, Tobias and Corso-Diaz, Ximena and Kwicklis, Madeline and van Asten, Freekje and Ratnapriya, Rinki and Chew, Emily Y. and Hernandez, Dena G. and Montezuma, Sandra R. and Ferrington, Deborah A. and Weber, Bernhard H. F. and Segre, Ayellet V. and Swaroop, Anand (2024) QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration. NATURE COMMUNICATIONS, 15 (1): 1972. ISSN 2041-1723
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; OXIDATIVE STRESS; EXPRESSION; INTEGRATION; EQTL; COLOCALIZATION; HERITABILITY; PROGRESSION; PROTEINS; GENOTYPE |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jan 2026 10:41 |
| Last Modified: | 27 Jan 2026 10:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64866 |
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