Journal article
Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy
Nature communications, Vol.8(1), 14898
03/30/2017
DOI: 10.1038/ncomms14898
PMCID: PMC5379100
PMID: 28358029
Abstract
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 ): 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.
Details
- Title: Subtitle
- Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy
- Creators
- Natalie A Afshari - Shiley Eye Institute, University of California, La Jolla, California 92093, USARobert P Igo Jr - Case Western Reserve UniversityNathan J Morris - Case Western Reserve UniversityDwight Stambolian - University of PennsylvaniaShiwani Sharma - Flinders UniversityV Lakshmi Pulagam - Case Western Reserve UniversitySteven Dunn - Michigan Cornea Consultants, PC, Southfield, Michigan 48034, USAJohn F Stamler - Department of Ophthalmology, University of Iowa, College of Medicine, Iowa City, Iowa 52242, USABarbara J Truitt - Case Western Reserve UniversityJacqueline Rimmler - Duke UniversityAbraham Kuot - Flinders UniversityChristopher R Croasdale - Davis Duehr Dean Clinic, Madison, Wisconsin 53715, USAXuejun Qin - Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina 27701, USAKathryn P Burdon - Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, AustraliaS Amer Riazuddin - The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USARichard Mills - Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, AustraliaSonja Klebe - Department of Pathology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, AustraliaMollie A Minear - Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina 27701, USAJiagang Zhao - University of California San DiegoElmer Balajonda - Duke University Eye Center, Duke University Medical Center, Durham, North Carolina 27710, USAGeorge O Rosenwasser - Central Pennsylvania Eye Institute, Hershey, Pennsylvania 17033, USAKeith H Baratz - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USAV Vinod Mootha - Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USASanjay V Patel - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USASimon G Gregory - Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina 27701, USAJoan E Bailey-Wilson - Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health and Johns Hopkins University, Baltimore, Maryland 21224, USAMarianne O Price - Price Vision Group, Indianapolis, Indiana 46260, USAJamie E Craig - Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, South Australia 5042, AustraliaJohn H Fingert - Department of Ophthalmology, University of Iowa, College of Medicine, Iowa City, Iowa 52242, USAJohn D Gottsch - The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USAAnthony J Aldave - Stein Eye Institute, University of California, Los Angeles, California 90095, USAGordon K Klintworth - Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USAJonathan H Lass - Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, Ohio 44106, USAYi-Ju Li - Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina 27710, USAFrancis W Price JrSudha K Iyengar - Department of Ophthalmology and Visual Sciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, Ohio 44106, USA
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.8(1), 14898
- DOI
- 10.1038/ncomms14898
- PMID
- 28358029
- PMCID
- PMC5379100
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- England
- Grant note
- P30 EY011373 / NEI NIH HHS P30 EY022589 / NEI NIH HHS UL1 RR024989 / NCRR NIH HHS R01 EY022082 / NEI NIH HHS R21 EY015145 / NEI NIH HHS R01 EY023196 / NEI NIH HHS HHSN268201200008I / NHLBI NIH HHS UL1 TR000439 / NCATS NIH HHS R01 EY016482 / NEI NIH HHS R01 EY016835 / NEI NIH HHS R01 EY016514 / NEI NIH HHS
- Language
- English
- Date published
- 03/30/2017
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980093802771
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