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

African ancestry Black genetic risk factors genome-wide association study glaucoma health disparities neurodegeneration ophthalmology optic nerve primary open-angle glaucoma

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
18 Jan 2024
Historique:
received: 05 04 2023
revised: 24 07 2023
accepted: 04 12 2023
medline: 20 1 2024
pubmed: 20 1 2024
entrez: 19 1 2024
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2023.12.006 PMID: 38242088
pubmed: 38242088
pii: S0092-8674(23)01338-7
doi: 10.1016/j.cell.2023.12.006
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

464-480.e10

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

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.

Auteurs

Shefali S Verma (SS)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Harini V Gudiseva (HV)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Venkata R M Chavali (VRM)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Rebecca J Salowe (RJ)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Yuki Bradford (Y)

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Lindsay Guare (L)

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Anastasia Lucas (A)

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

David W Collins (DW)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Vrathasha Vrathasha (V)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Rohini M Nair (RM)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Sonika Rathi (S)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Bingxin Zhao (B)

Department of Statistics and Data Science, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA.

Jie He (J)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Roy Lee (R)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Selam Zenebe-Gete (S)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Anita S Bowman (AS)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Caitlin P McHugh (CP)

New York Genome Center, New York, NY, USA.

Michael C Zody (MC)

New York Genome Center, New York, NY, USA.

Maxwell Pistilli (M)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Naira Khachatryan (N)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Ebenezer Daniel (E)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Windell Murphy (W)

Windell Murphy, MD, Philadelphia, PA, USA.

Jeffrey Henderer (J)

Department of Ophthalmology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Tarrytown, NY, USA.

Tyler G 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.

Sudha K 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.

Neal S Peachey (NS)

Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA; Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.

Kent D 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.

Xiuqing 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.

Yii-Der Ida 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.

Linda Zangwill (L)

Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, USA.

Christopher Girkin (C)

Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Radha Ayyagari (R)

Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, USA.

Jeffrey Liebmann (J)

Department of Ophthalmology, Columbia University Medical Center, Columbia University, New York, NY, USA.

Chimd M Chuka-Okosa (CM)

Department of Ophthalmology, University of Nigeria, Ituku, Nigeria.

Susan E Williams (SE)

Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa.

Stephen Akafo (S)

Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, Ghana.

Donald L Budenz (DL)

Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, USA.

Olusola O Olawoye (OO)

Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria.

Michele Ramsay (M)

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Adeyinka Ashaye (A)

Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria.

Onoja M Akpa (OM)

Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan, Ibadan, Nigeria.

Tin Aung (T)

Singapore Eye Research Institute, Singapore, Singapore.

Janey L Wiggs (JL)

Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.

Ahmara G Ross (AG)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Qi N Cui (QN)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Victoria Addis (V)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Amanda Lehman (A)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Eydie Miller-Ellis (E)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Prithvi S Sankar (PS)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Scott M Williams (SM)

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.

Gui-Shuang Ying (GS)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jessica 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.

Jerome I 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.

Robert Weinreb (R)

Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, USA.

Chiea Chuen Khor (CC)

Genome Institute of Singapore, Singapore, Singapore.

Michael A Hauser (MA)

Department of Medicine, Duke University, Durham, NC, USA.

Marylyn D Ritchie (MD)

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Joan M O'Brien (JM)

Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: joan.o'brien@pennmedicine.upenn.edu.

Classifications MeSH