A Genome-Wide Association Study of Optic Disc Parameters:
“Author Summary

Morphologic characteristics of the optic nerve head are involved in many ophthalmic diseases. Its size, called the optic disc area, is an important measure and has been associated with e.g. myopia and open-angle glaucoma (OAG). Another important and clinical parameter of the optic disc is the vertical cup-disc ratio (VCDR). Although studies have shown a high heritability of optic disc area and VCDR, its genetic determinants are still undetermined. We therefore conducted a genome-wide association (GWA) study on these quantitative traits, using data of over 11,000 Caucasian participants, and related the findings to myopia and OAG. We found evidence for association of three loci with optic disc area: CDC7/TGFBR3 region, ATOH7, and SALL1; and six with VCDR: CDKN2B, SIX1, SCYL1, CHEK2, ATOH7, and DCLK1; and additionally one borderline significant locus: BCAS3. None of the loci could be related to myopia. There was marginal evidence for association of ATOH7, CDKN2B, and SIX1 with OAG, which remains to be confirmed. The present study reveals new insights into the physiological development of the optic nerve and may shed light on the pathophysiological protein pathways leading to (neuro-) ophthalmologic diseases such as OAG.