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Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.


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 × 10-8): 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.

SUBMITTER: Afshari NA 

PROVIDER: S-EPMC5379100 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.

Afshari Natalie A NA   Igo Robert P RP   Morris Nathan J NJ   Stambolian Dwight D   Sharma Shiwani S   Pulagam V Lakshmi VL   Dunn Steven S   Stamler John F JF   Truitt Barbara J BJ   Rimmler Jacqueline J   Kuot Abraham A   Croasdale Christopher R CR   Qin Xuejun X   Burdon Kathryn P KP   Riazuddin S Amer SA   Mills Richard R   Klebe Sonja S   Minear Mollie A MA   Zhao Jiagang J   Balajonda Elmer E   Rosenwasser George O GO   Baratz Keith H KH   Mootha V Vinod VV   Patel Sanjay V SV   Gregory Simon G SG   Bailey-Wilson Joan E JE   Price Marianne O MO   Price Francis W FW   Craig Jamie E JE   Fingert John H JH   Gottsch John D JD   Aldave Anthony J AJ   Klintworth Gordon K GK   Lass Jonathan H JH   Li Yi-Ju YJ   Iyengar Sudha K SK  

Nature communications 20170330


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 nov  ...[more]

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