Genetics of Myopia in a Participant Driven, Web-Based Cohort. A. K. Kiefer, J. Y. Tung, C. Do, D. A. Hinds, J. L. Mountain, U. Francke, N. Eriksson 23andMe, Inc., Mountain View, CA.
Myopia, or nearsightedness, is the most common eye disorder worldwide. Myopia results from the elongation of the eye axis, which causes images to be focused in the vitreous part of the eye instead of on the retina. In the United States, roughly a third of the adult population has clinically relevant myopia (more severe than -1 diopter), and its prevalence has increased in recent decades. The etiology of myopia is largely unknown, but is believed to have a substantial genetic component, with prior heritability estimates ranging from 0.60-0.90. Education, reading, and lack of time spent outdoors are known environmental risk factors for myopia, and may contribute to its rapidly increasing prevalence. We collected self-reported information on myopia from the 23andMe participant cohort. We describe the results of a genome-wide association analysis on this convenience sample consisting of approximately 23,000 cases, defined as anyone who reported a diagnosis of nearsightedness, and 16,000 controls, who reported that they had not been diagnosed with nearsightedness, all of European ancestry. We replicate the only two previously identified associations with myopia in Europeans, in GOLGA8B, which belongs to a family of Golgi auto-antigens, and in RASGRFI, a transcription initiation site that is highly expressed in neurons and the retina. We also find novel genome-wide-significant associations (P < 5E-08) in 13 regions. Notable among the novel findings are variants in LAMA2 (rs12193446,) a gene coding for laminin, an extracellular protein that is a major component of the basement membrane and believed to be involved in the development and maintenance of different eye structures; in RDH5 (rs3138142), which encodes a retinol dehydrogenase that catalyzes the final step in the biosynthesis of 11-cis retinaldehyde; and in KCNQ5 (rs7744813), a member of the KCNQ potassium channel gene family that produces an M-type K(+) current channel and is expressed in monkey retinal pigmentation epithelial cells. This largest ever GWAS on myopia in Europeans--by an order of magnitude--identifies many new potential biological pathways involved in the development of myopia.