Variants near EGFR on CFA18 are associated with risk of chronic superficial keratitis in the Australian Racing Greyhound

Chronic superficial keratitis (CSK) is a progressive inflammatory condition of the eye and cornea can cause discomfort and blindness. Variation in disease risk across dog breeds strongly suggests that CSK has a genetic basis. In addition to genetic risk, the occurrence of CSK is exacerbated by exposure to ultraviolet light. Genome-wide association analysis considered 109 Greyhounds, 70 with CSK and the remainder with normal phenotype at an age over four years. Three co-located variants on CFA18 near the 5’ region of the Epidermal Growth Factor Receptor (<em>EGFR</em>) gene were associated with genome-wide significance after multiple-test correction [(BICF2P579527, CFA18:5,954,402, praw=1.765e-07, pgenome= 0.017); (BICF2P1310662, CFA18:5,963,278, praw=4.09e-07, pgenome= 0.040); (BICF2P160719, CFA18:5,973,238, praw= 4.09e-07, pgenome= 0.040)] (canFam3.1). Of the top 10 associated markers, eight were co-located with the significantly associated markers on CFA18. The associated haplotype on CFA18 is protective for the CSK condition. <em>EGFR </em>is known to play a role in corneal healing, where it initiates differentiation and proliferation of epithelial cells that in turn signal the involvement of stromal keratocytes to commence apoptosis. Further validation of the associated variants is required prior to their use in genetic testing for breeding programs.