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A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.
Verma, Shefali S; Gudiseva, Harini V; Chavali, Venkata R M; Salowe, Rebecca J; Bradford, Yuki; Guare, Lindsay; Lucas, Anastasia; Collins, David W; Vrathasha, Vrathasha; Nair, Rohini M; Rathi, Sonika; Zhao, Bingxin; He, Jie; Lee, Roy; Zenebe-Gete, Selam; Bowman, Anita S; McHugh, Caitlin P; Zody, Michael C; Pistilli, Maxwell; Khachatryan, Naira; Daniel, Ebenezer; Murphy, Windell; Henderer, Jeffrey; Kinzy, Tyler G; Iyengar, Sudha K; Peachey, Neal S; Taylor, Kent D; Guo, Xiuqing; Chen, Yii-Der Ida; Zangwill, Linda; Girkin, Christopher; Ayyagari, Radha; Liebmann, Jeffrey; Chuka-Okosa, Chimd M; Williams, Susan E; Akafo, Stephen; Budenz, Donald L; Olawoye, Olusola O; Ramsay, Michele; Ashaye, Adeyinka; Akpa, Onoja M; Aung, Tin; Wiggs, Janey L; Ross, Ahmara G; Cui, Qi N; Addis, Victoria; Lehman, Amanda; Miller-Ellis, Eydie; Sankar, Prithvi S; Williams, Scott M.
Afiliação
  • 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.
Cell ; 187(2): 464-480.e10, 2024 01 18.
Article em En | MEDLINE | ID: mdl-38242088
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glaucoma de Ângulo Aberto / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glaucoma de Ângulo Aberto / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2024 Tipo de documento: Article