The Genetics of Myopia

Myopia is generally classified as mild/moderate/common and extreme. Someone with mild myopia may have trouble seeing objects that are farther away, but can generally still function at the daily tasks, where as an extremely nearsighted person can only clearly see objects that are very close to the eyes.The degree of myopia is determined using diopters (D, measures the focusing power of a lens). Diopters over 6.0 is determined as high myopia, and diopters between 1.0 – 3.0 is termed mild.

Myopia usually develops in childhood and the early teen years. A child or teenager may present myopia symptoms if he squints or frowns when trying to concentrate on an object far away, or he holds the object very close to the face. The individual may also prefer sitting very near to the TV or computer, or at the front of the classroom.

Identifying the genes influencing myopia could help develop targeted treatments for children who are genetically predisposed to developing myopia. Twin and family studies strongly indicate that myopia is highly heritable. The prevalence of myopia is greater in children of myopic parents than children of nonmyopic parents. On the other hand, various studies in epidemiology have shown that myopia is associated with certain behaviors (environment) like near-work, intensive studying and reading. Myopia is highly prevalent in certain populations like the Asian Chinese, Japanese and Ashkenazi Jewish males. Because of its complex inheritance, finding the genes for myopia susceptibility has been a challenge, but not impossible.

One of the first myopia loci to be mapped was on chromosome Xq28 (named MYP1) from a family with X-linked recessive form of myopia. The syndrome was later renamed as the Bornholm eye disease, and includes myopia, lazy eyes and red-green color blindness in its diagnosis.

The strongest evidence for autosomal myopia loci came from studies that looked at independent extended families with dominant high myopia (over 6.0 diopters). Three separate studies mapped susceptibility loci to chromosome 18q11.3 (MYP2), chromosome 12q21-23 (MYP3) and chromosome 17q21-22. These studies show that different genes could be causing myopia in different families.

Early studies on mild myopia showed that the genes for high myopia (on chromosome 18 and 12) did not play roles in causing the milder forms.

Evidence for a new region on chromosome 22 was found when extended families of the Ashkenazi Jews and the Amish community in Lancaster, Pennsylvania were studied. The two populations are homogenous, meaning genetic diversity is much lower compared to the average US population. Because the populations are rather isolated from outside communities, environmental influence is very similar inside compared to the US as a whole. These characteristics make for very good populations to study when looking at complex traits. Researchers want as little diversity as possible to isolate the cause of the disease.

Using quantitative measurement of refraction (instead of presence or absence of myopia), a twin study in London provided another evidence for a candidate gene on chromosome 11, at the precise location of the PAX6 gene. PAX6 (homeobox gene) is known as a master-control for eye development and other neural functions, so there is much promise of finding a gene or genes in this region.

None of the chromosome regions so far identified have presented a specific gene for myopia. The next steps to verifying the above results involve increasing the number of families followed, confirming the results in other populations using the same definitions of myopia, performing analyses on more markers within a shorter region of the genome, and using single nucleotide polymorphisms to identify associations with the disease. Myopia is only one example of the challenge of the genetics of complex diseases. But the technologies are rapidly evolving that enable scientists to identify potential locus in smaller regions, so finding the genes for myopia is truly promising.

Dissecting the Genetics of Human High Myopia: A Molecular Biologic Approach

Terri L Young, MD. Trans Am Ophthalmol Soc. 2004 December; 102: 423–446.

Myopia genetics update: Unlocking the secrets of myopia. http://www.otmagazine.co.uk/articles/docs/b5dd840cfce771afd00409348ce87a66_guggenheim20040910.pdf