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Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.
Afshari, Natalie A; Igo, Robert P; Morris, Nathan J; Stambolian, Dwight; Sharma, Shiwani; Pulagam, V Lakshmi; Dunn, Steven; Stamler, John F; Truitt, Barbara J; Rimmler, Jacqueline; Kuot, Abraham; Croasdale, Christopher R; Qin, Xuejun; Burdon, Kathryn P; Riazuddin, S Amer; Mills, Richard; Klebe, Sonja; Minear, Mollie A; Zhao, Jiagang; Balajonda, Elmer; Rosenwasser, George O; Baratz, Keith H; Mootha, V Vinod; Patel, Sanjay V; Gregory, Simon G; Bailey-Wilson, Joan E; Price, Marianne O; Price, Francis W; Craig, Jamie E; Fingert, John H; Gottsch, John D; Aldave, Anthony J; Klintworth, Gordon K; Lass, Jonathan H; Li, Yi-Ju; Iyengar, Sudha K.
Afiliação
  • Afshari NA; Shiley Eye Institute, University of California, La Jolla, California 92093, USA.
  • Igo RP; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
  • Morris NJ; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
  • Stambolian D; Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
  • Sharma S; Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, Australia.
  • Pulagam VL; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
  • Dunn S; Michigan Cornea Consultants, PC, Southfield, Michigan 48034, USA.
  • Stamler JF; Department of Ophthalmology, University of Iowa, College of Medicine, Iowa City, Iowa 52242, USA.
  • Truitt BJ; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
  • Rimmler J; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina 27701, USA.
  • Kuot A; Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, Australia.
  • Croasdale CR; Davis Duehr Dean Clinic, Madison, Wisconsin 53715, USA.
  • Qin X; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina 27701, USA.
  • Burdon KP; Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, Australia.
  • Riazuddin SA; Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, Australia.
  • Mills R; The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
  • Klebe S; Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, Australia.
  • Minear MA; Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, Australia.
  • Zhao J; Department of Pathology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, Australia.
  • Balajonda E; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina 27701, USA.
  • Rosenwasser GO; Shiley Eye Institute, University of California, La Jolla, California 92093, USA.
  • Baratz KH; Duke University Eye Center, Duke University Medical Center, Durham, North Carolina 27710, USA.
  • Mootha VV; Central Pennsylvania Eye Institute, Hershey, Pennsylvania 17033, USA.
  • Patel SV; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Gregory SG; Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
  • Bailey-Wilson JE; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Price MO; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina 27701, USA.
  • Price FW; Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health and Johns Hopkins University, Baltimore, Maryland 21224, USA.
  • Craig JE; Price Vision Group, Indianapolis, Indiana 46260, USA.
  • Fingert JH; Price Vision Group, Indianapolis, Indiana 46260, USA.
  • Gottsch JD; Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, Australia.
  • Aldave AJ; Department of Ophthalmology, University of Iowa, College of Medicine, Iowa City, Iowa 52242, USA.
  • Klintworth GK; The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
  • Lass JH; Stein Eye Institute, University of California, Los Angeles, California 90095, USA.
  • Li YJ; Duke University Eye Center, Duke University Medical Center, Durham, North Carolina 27710, USA.
  • Iyengar SK; Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nat Commun ; 8: 14898, 2017 03 30.
Article em En | MEDLINE | ID: mdl-28358029
The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10-8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Distrofia Endotelial de Fuchs / Estudo de Associação Genômica Ampla / Loci Gênicos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Distrofia Endotelial de Fuchs / Estudo de Associação Genômica Ampla / Loci Gênicos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos