ArticleNature communications2025
HTRA1/lncRNA HTRA1-AS1 dominates in age-related macular degeneration reticular pseudodrusen genetic risk with no complement involvement.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Authors and funding
52 authors.
Samaneh FarashiPopulation Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Carla J Abbott *Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-1432-8977
Brendan R E Ansell *Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0003-0297-897X
Zhichao Wu *Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
Lebriz AltayDepartment of Ophthalmology, Faculty of Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany.
Ella ArnonDepartment of Ophthalmology, Duke University Medical Centre, Durham, NC, USA.
Louis ArnouldOphthalmology Department, University Hospital, Dijon, France.
Yelena BagdasarovaDepartment of Ophthalmology, University of Washington, Seattle, WA, USA.
Konstantinos BalaskasMoorfields Eye Hospital NHS Foundation Trust, University College London Institute of Ophthalmology, London, UK.
Fred K ChenDepartment of Surgery (Ophthalmology), The University of Melbourne, East Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0003-2809-9930
Emily ChewDivision of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0999-9802
Itay ChowersDepartment of Ophthalmology, Hadassah Medical Centre and the Hebrew University of Jerusalem, Jerusalem, Israel.
Steven ClarkeComputational Sciences, Genentech Inc, South San Francisco, California, USA.ORCID http://orcid.org/0000-0002-2706-4448
Catherine CukrasUnit on Clinical Investigation of Retinal Diseases, National Eye Institute, National Institute of Health, Bethesda, MD, USA.
Cécile DelcourtUniversity of Bordeaux, INSERM, BPH, Bordeaux, France.ORCID http://orcid.org/0000-0002-2099-0481
Marie-Noëlle DelyferUniversity of Bordeaux, INSERM, BPH, Bordeaux, France.ORCID http://orcid.org/0000-0002-3127-8617
Anneke I den HollanderDepartment of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0003-0634-5408
Sascha FauserDepartment of Ophthalmology, Faculty of Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany.
Robert P FingerDepartment of Ophthalmology, University Hospital Bonn, Bonn, Germany.
Pierre-Henry GabrielleOphthalmology Department, University Hospital, Dijon, France.ORCID http://orcid.org/0000-0002-9688-4845
Jiru HanPopulation Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Lauren A B HodgsonCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-9492-3927
Ruth HoggCentre for Public Health, Queen's University Belfast Faculty of Medicine Health and Life Sciences, Belfast, UK.ORCID http://orcid.org/0000-0001-9413-2669
Frank G HolzDepartment of Ophthalmology, University Hospital Bonn, Bonn, Germany.
Carel HoyngDepartment of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.
Himeesh KumarCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0001-9169-5335
Eleonora M LadDepartment of Ophthalmology, Duke University Medical Centre, Durham, NC, USA.
Aaron LeeDepartment of Ophthalmology, University of Washington, Seattle, WA, USA.
Ulrich F O LuhmannRoche Pharmaceutical Research and Early Development, Translational Medicine Ophthalmology, Roche Innovation Center, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1993-1951
Matthias M MauschitzDepartment of Ophthalmology, University Hospital Bonn, Bonn, Germany.
Amy J McKnightCentre for Public Health, Queen's University Belfast Faculty of Medicine Health and Life Sciences, Belfast, UK.ORCID http://orcid.org/0000-0002-7482-709X
Samuel McLenachanCentre of Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Perth, WA, Australia.ORCID http://orcid.org/0000-0001-5732-7387
Aniket MishraUniversity of Bordeaux, INSERM, BPH, Bordeaux, France.ORCID http://orcid.org/0000-0002-8141-1543
Ismail MoghulMoorfields Eye Hospital NHS Foundation Trust, University College London Institute of Ophthalmology, London, UK.ORCID http://orcid.org/0000-0003-3653-2327
Luz D OrozcoComputational Sciences, Genentech Inc, South San Francisco, California, USA.ORCID http://orcid.org/0000-0002-2541-9866
Danuta M SampsonCentre of Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Perth, WA, Australia.ORCID http://orcid.org/0000-0003-4737-6606
Liam W ScottPopulation Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
Vasilena SitnilskaDepartment of Ophthalmology, Faculty of Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0002-0886-4263
Scott SongDepartment of Ophthalmology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0009-0008-5861-5709
Amy StockwellDepartment of Human Genetics, Genentech Inc., South San Francisco, CA, USA.
Anand SwaroopNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1975-1141
Jan H TerheydenDepartment of Ophthalmology, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-0174-4066
Liran TiosanoDepartment of Ophthalmology, Hadassah Medical Centre and the Hebrew University of Jerusalem, Jerusalem, Israel.
Adnan TufailMoorfields Eye Hospital NHS Foundation Trust, University College London Institute of Ophthalmology, London, UK.ORCID http://orcid.org/0000-0001-6131-7640
Brian L YaspanDepartment of Human Genetics, Genentech Inc., South San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3787-2510
MACUSTAR consortium
NICOLA consortium
Alice PébayDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0002-7408-9453
Erica L FletcherDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-9412-9523
Robyn H GuymerCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia. rh.guymer@unimelb.edu.au.ORCID http://orcid.org/0000-0002-9441-4356
Melanie BahloPopulation Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. bahlo@wehi.edu.au.ORCID http://orcid.org/0000-0001-5132-0774
Reticular Pseudodrusen Consortium
Funding
Monocytes in Dry Age-Related Macular DegenerationK23EY026988 · NEI · DUKE UNIVERSITY · PI LAD, ELEONORA GEORGETA · 2016 to 2018
$420kDepartment of Health | National Health and Medical Research Council (NHMRC) GNT1154389Department of Health | National Health and Medical Research Council (NHMRC) GNT1157776Department of Health | National Health and Medical Research Council (NHMRC) GNT1181010Department of Health | National Health and Medical Research Council (NHMRC) GNT1194667Department of Health | National Health and Medical Research Council (NHMRC) GNT1195236Department of Health | National Health and Medical Research Council (NHMRC) GNT2008382Department of Health | National Health and Medical Research Council (NHMRC) Independent Research Institute Infrastructure Support SchemeDepartment of Health, State Government of Victoria (Victorian Department of Health) Operational Infrastructure SupportNEI NIH HHS K23 EY026988U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) Z01EY000546
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.
Indexed as
High-Temperature Requirement A Serine Peptidase 1Macular DegenerationRetinal DrusenRNA, Long NoncodingAgedAged, 80 and overChromosomes, Human, Pair 1Chromosomes, Human, Pair 10FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideProteinsARMS2 protein, humanHigh-Temperature Requirement A Serine Peptidase 1HTRA1 protein, humanProteinsRNA, Long Noncoding
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