HTRA1/lncRNA HTRA1-AS1 dominates in age-related macular degeneration reticular pseudodrusen genetic risk with no complement involvement
Year: 2025
Type: article
Study design: Observational Study
Abstract: Age-related macular degeneration (AMD) is a multifactorial retinal disease with a large genetic risk contribution. Reticular pseudodrusen (RPD) is a sub-phenotype of AMD with a high risk of progression to late vision threatening AMD. In a genome-wide association study of 2165 AMD+/RPD+ and 4181 AMD+/RPD- compared to 7639 control participants, both chromosomes 1 (CFH) and 10 (ARMS2/HTRA1) major AMD risk loci are reidentified. However association is only detected for the chromosome 10 locus when comparing AMD+/RPD+ to AMD+/RPD- cases. The chromosome 1 locus is notably absent. The chromosome 10 RPD risk region contains a long non-coding RNA HTRA1-AS1 (ENSG00000285955/BX842242.1) which colocalizes with genetic markers of retinal thickness. HTRA1-AS1 has a strong retinal eQTL signal, pinpointing the parafoveal photoreceptor outer segment layer. Whole genome sequencing of phenotypically extreme RPD cases identifies even stronger enrichment for the chromosome 10 risk genotype.
Source: Nature Communications
Authors: Samaneh Farashi, Carla J. Abbott, Brendan R. E. Ansell, Zhichao Wu, Lebriz Altay, Ella Arnon, Louis Arnould, Yelena Bagdasarova, Konstantinos Balaskas, Fred K. Chen, Emily Chew, Itay Chowers, Steven Clarke, Catherine Cukras, Cécile Delcourt, Marie-Noëlle Delyfer, Anneke I. den Hollander, Sascha Fauser, Robert P. Finger, Pierre-Henry Gabrielle, Jiru Han, Lauren A. B. Hodgson, Ruth Hogg, Frank G. Holz, Carel Hoyng, Himeesh Kumar, Eleonora M. Lad, Aaron Lee, Ulrich F. O. Luhmann, Matthias M. Mauschitz, Amy J. McKnight, Samuel McLenachan, Aniket Mishra, Ismail Moghul, Luz D. Orozco, Danuta M. Sampson, Liam W. Scott, Vasilena Sitnilska, Scott Song, Amy Stockwell, Anand Swaroop, Jan H. Terheyden, Liran Tiosano, Adnan Tufail, Brian L. Yaspan, L. Altay, A. Tufail, C. B. Hoyng, U. F. O. Luhmann, R. P. Finger, F. G. Holz, J. H. Terheyden, R. Hogg, A. J. McKnight, Alice Pébay, Erica L. Fletcher, Robyn H. Guymer, Melanie Bahlo, Anneke I. den Hollander
Institutions: The University of Melbourne, Walter and Eliza Hall Institute of Medical Research, The Royal Victorian Eye & Ear Hospital, Centre for Eye Research Australia, Duke University, University of Cologne, Duke Medical Center, University Hospital Cologne, Université de Bourgogne, University of Washington, Moorfields Eye Hospital NHS Foundation Trust, University College London, Lions Eye Institute, National Institutes of Health, The University of Western Australia, Royal Perth Hospital, National Eye Institute, Hebrew University of Jerusalem, Hadassah Medical Center, Genentech, Université de Bordeaux, Inserm, Bordeaux Population Health, Radboud University Medical Center, Centre Hospitalier Universitaire de Bordeaux, AbbVie (United States), F. Hoffmann-La Roche AG, University Hospital Bonn, Heidelberg University, Medizinische Fakultät Mannheim, Centre National de la Recherche Scientifique, Université Bourgogne Franche-Comté, Centre des Sciences du Goût et de l'Alimentation, Queen's University Belfast, The Royal Melbourne Hospital
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, Office of Dietary Supplements, Sanofi, Canon Foundation for Scientific Research, European Federation of Pharmaceutical Industries and Associations, Fondation Vaincre Alzheimer, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Department of Health, State Government of Victoria, Fondation de France, Université de Bordeaux, Mutuelle Générale de l'Education Nationale, Fondation Voir et Entendre, National Institutes of Health, Genentech, Medical Research Council, National Health and Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Eye Institute, National Center for Complementary and Alternative Medicine, National Institute of Neurological Disorders and Stroke, National Center for Complementary and Integrative Health
Awards: G1030008072, G1281606662, G1283799130, The brain resilience initiative: genes shielding the brain from cerebrovascular insults, G1598674636, G1837968366, Gene discovery and functional insights for neurological and retinal disorders, G2821799245, Monocytes in Dry Age-Related Macular Degeneration, G2958376014, G3185890188, G416392098, G4261046840, G434337789, G4813868611, G4816331716, A pathway to translation: uncovering novel causes, genetic associations and potential intervention strategies for age related macular degeneration, G4993659640, Epitranscriptomics in neurological disease, G5206984971, G5389958763, G5847831411, G5901555535, G6237749715, G6370100934, Human induced pluripotent stem cells to understand neurodegeneration, G6463773, Develop and validate appropriate and acceptable outcome measures in intermediate age-related macular degeneration for future interventional clinical trials - Sofia ref.: 116076, G6771372278, G6881768649, G7468482971, Preventing Irreversible Vision Loss from Age-Related Macular Degeneration , G849075540, Multidimensional interrogation of microvascular matrisome abnormalities in cerebral small vessel diseases, G8885395095, G8973918369
OpenAlex ID: W4417112755