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

Natalie Afshari, Robert Igo, Nathan Morris, Dwight Stambolian, Shiwani Sharma, Lakshmi V, Steven Dunn, John Stamler, Barbara Truitt, Jacqueline Rimmler, Abraham Kuot, Xuejun Qin, Christopher Croasdale, Kathryn Burdon, S Riazuddin, Richard Mills, Sonja Klebe, Mollie Minear, Jiagang Zhao, Elmer BalajondaGeorge Rosenwasser, Keith Baratz, V Mootha, Sanjay Patel, Simon Gregory, Joan Bailey-Wilson, Marianne Price, Francis Price, Jamie Craig, John Fingert, John Gottsch, Anthony Aldave, Gordon Klintworth, Jonathan Lass, Yi Li, Sudha Iyengar

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)


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.

Original languageEnglish
Article number14898
Number of pages8
JournalNature Communications
Publication statusPublished - 30 Mar 2017


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