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Three Additional Gene Loci Associated with Corneal Disease FECD

Corneal diseases are among the most common causes of visual impairment and blindness, with Fuchs endothelial corneal dystrophy (FECD), a gradual swelling and clouding of the cornea, being the most common reason for eventual corneal transplants. In work reported online on March 30,2017 in Nature Communications, researchers at the University of California San Diego School of Medicine, with colleagues at Case Western University, Duke University, the National Institutes of Health and elsewhere, have identified three novel genomic loci linked to FECD, which often clusters in families and is roughly 39 percent heritable. The open-acccess article is titled “Genome-Wide Association Study Identifies Three Novel Loci in Fuchs Endothelial Corneal Dystrophy.” “Previously, there was one known FECD locus. We've expanded that number to four," said the study's first author Natalie A. Afshari, M.D., Professor of Ophthalmology, Stuart Brown M.D. Chair in Ophthalmology in Memory of Donald Shiley, and Chief of Cornea and Refractive Surgery at the Shiley Eye Institute at UC San Diego Health. "These findings provide a deeper understanding of the pathology of FECD, which in turn will help us develop better therapies for treating or preventing this disabling disease." FECD affects the innermost layer of cells in the cornea (the transparent front cover of the eye), called the endothelium. The endothelium is responsible for maintaining the proper amount of fluid in the cornea, keeping it clear. FECD is a progressive disorder in which the endothelium slowly degrades, with lost clarity, pain, and severely impaired vision. It affects 4 percent of the U.S. population above age 40 and worsens with age. Women are two to four times more frequently affected than men. While there is symptomatic treatment in early stages, surgery -- often a corneal transplant -- is the only remedy after significant vision loss occurs.

The research team conducted a genome-wide association study (GWAS), an analytical approach in which scientists look for genetic variants in individuals associated with a particular disease. This study involved 1,404 patients with FECD and 2,564 controls of European ancestry.

The results confirmed the known role of the TCF4 gene, but also revealed associations with three other loci: KANK4, LAMC1, and LINC009970/ATPB1. Researchers also found some genomic markers that were more associated by gender, with LAMC1 increasing FECD risk in women, and TCF4 increasing risk in men.

"While more work must be done to precisely elucidate what these proteins do," said Dr. Afshari, "the results suggest they have essential roles in sustaining and maintaining the health of the corneal endothelium. This knowledge improves our understanding of the genetic risk factors for FECD and gives us new therapeutic targets."

[Press release] [Nature Communications article]