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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.
Afiliación
  • Advani J; Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Mehta PA; Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.
  • Hamel AR; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
  • Mehrotra S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kiel C; Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.
  • Strunz T; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
  • Corso-Díaz X; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kwicklis M; Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.
  • van Asten F; Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
  • Ratnapriya R; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chew EY; Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
  • Hernandez DG; Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
  • Montezuma SR; Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Ferrington DA; Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Weber BHF; Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Segrè AV; Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
  • Swaroop A; Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Nat Commun ; 15(1): 1972, 2024 Mar 04.
Article en En | MEDLINE | ID: mdl-38438351
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Degeneración Macular Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Degeneración Macular Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido