A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Autor:	Verma SS; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Gudiseva HV; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Chavali VRM; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Salowe RJ; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Bradford Y; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Guare L; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lucas A; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Collins DW; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Vrathasha V; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Nair RM; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Rathi S; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Zhao B; Department of Statistics and Data Science, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA., He J; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lee R; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Zenebe-Gete S; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Bowman AS; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., McHugh CP; New York Genome Center, New York, NY, USA., Zody MC; New York Genome Center, New York, NY, USA., Pistilli M; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Khachatryan N; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Daniel E; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Murphy W; Windell Murphy, MD, Philadelphia, PA, USA., Henderer J; Department of Ophthalmology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA., Kinzy TG; Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA., Iyengar SK; Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA., Peachey NS; Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA., Taylor KD; Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Guo X; Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Chen YI; Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Zangwill L; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, USA., Girkin C; Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Ayyagari R; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, USA., Liebmann J; Department of Ophthalmology, Columbia University Medical Center, Columbia University, New York, NY, USA., Chuka-Okosa CM; Department of Ophthalmology, University of Nigeria, Ituku, Nigeria., Williams SE; Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa., Akafo S; Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, Ghana., Budenz DL; Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, USA., Olawoye OO; Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria., Ramsay M; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Ashaye A; Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria., Akpa OM; Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan, Ibadan, Nigeria., Aung T; Singapore Eye Research Institute, Singapore, Singapore., Wiggs JL; Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA., Ross AG; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Cui QN; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Addis V; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lehman A; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Miller-Ellis E; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Sankar PS; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Williams SM; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Ying GS; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Cooke Bailey J; Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Department of Pharmacology and Toxicology, Center for Health Disparities, Brody School of Medicine. East Carolina University, Greenville, NC, 27834, USA., Rotter JI; Department of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Weinreb R; Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, USA., Khor CC; Genome Institute of Singapore, Singapore, Singapore., Hauser MA; Department of Medicine, Duke University, Durham, NC, USA., Ritchie MD; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., O'Brien JM; Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: joan.o'brien@pennmedicine.upenn.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Jan 18; Vol. 187 (2), pp. 464-480.e10.
DOI:	10.1016/j.cell.2023.12.006
Abstrakt:	Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease. Competing Interests: Declaration of interests J.M.O. is a member of the scientific advisory board of Life Biosciences and a paid consultant of Atheneum Partners, Cerner Enviza (includes Kantar Health), and Calico. A.G.R. holds intellectual property for the use of gene therapy to treat glaucoma. E.M.-E. is a scientific advisor for Avisi and a paid consultant of Aerie Pharmaceuticals, Allergan, Eyenovia, and Thea Pharma. J.L. receives instrument support from Carl Zeiss Meditech, Inc., and Heidelberg Engineering, GmBH; receives research support from Novartis, Inc.; and is a paid consultant at Thea, Inc., Alcon Laboratories, Inc., Johnson & Johnson, Inc., Abbvie, Inc., Carl Zeiss Meditech, Inc., Genetech, Inc., and ONL Therapeutics, Inc. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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