Family Myopia Study

Myopia or nearsightedness, a condition that results in the inability to see distant objects
clearly, affects one in four Americans and is the most common eye disorder in the world with
an enormous public health and economic impact. Depending on epidemiologic definition, 3-19%
of acquired blindness has been ascribed to myopia. Evidence exists that myopia is a complex
disorder with a significant genetic component as well as potential environmental influences.
Implicating genetic factors, Sorsby et al. found that the trait correlation for monozygotic
twins was nearly twice that for dizygotic twins and zero for control pairs. A study, by Chen
et al., of Chinese twin pairs found a higher concordance rate of myopia (92.2%) for
monozygotic twins with concordant close-work habits, or differences of less than one hour per
day spent studying or reading, as compared to monozygotic twins with discordant close-work
habits (79.3%). The two studies suggest additive interaction between zygosity and close-work
habits.

Since there is a tendency of myopia to cluster in families, studying families with myopia
opens the possibility to identify any gene(s) responsible for the pathogenesis of myopia.
These genes could provide molecular tools for investigation of inherited myopia and may also
provide a starting point for elucidating mechanisms for the influence of near work on the
progression of myopia. The goal of this proposal is to identify regions of the human genome
that contain the genes responsible for non-syndromic myopia utilizing pedigrees identified by
the Myopia Family Study and genotypes generated by Dr. Dwight Stambolian's laboratory at the
University of Pennsylvania as well as by the Center for Inherited Disease Research. Pedigree
collection is ongoing in several geographic regions including Lakewood, NJ, for the
collection of Orthodox Jewish families, Lancaster County, PA for the collection of Amish
families, and Philadelphia, for recruitment of families of African American or Chinese
American background. Pedigrees of Caucasian descent have also been collected in Philadelphia.
All data collection is under the direction of Dr. Stambolian and funded by his grant from the
NEI; no NHGRI funds are being used for data collection, and NHGRI investigators do not have
any contact with study subjects. Because this disorder is complex and has a high likelihood
of being caused by multiple loci, multiple parametric and non-parametric methods of analysis
will be employed. Heterogeneity will be taken into account during these analyses, as will
environmental covariates, such as the effect of near work, when possible.

- INCLUSION CRITERIA:

The subject population will be adult individuals and their children, in good health with
the exception of myopia.

Subjects will be chosen based upon vision history of their extended family.

Preferred subjects will be those who have a family in which myopia passes through several
generations along one parent s side only, in which more than one sibling is affected with
myopia, but in which no more than one parent is affected.

Specific eligibility requirements for the index case include:

1. Cycloplegic refraction of 1.00 spherical equivalent (as long as there was 1.00D or
higher in each meridian if astigmatism is present) or worse in both eyes in those
under age 50 to be considered myopic;

2. Manifest refraction of 1.00 spherical equivalent (as long as there was 1.00D or higher
in each meridian if astigmatism is present) or worse in both eyes in those over age 50
to be considered myopic;

3. No history of systemic or ocular disease which might predispose to myopia including
premature birth;

4. The index case should have a familial history of myopia in either their parents or
children or other close relatives (suggesting a genetic influence);

5. In the event that the parents of the index case have myopia, it is preferred that only
one parent be affected with myopia.

Some of these bilineal families may be collected if necessary to achieve the desired sample
size, but unilateral families are preferred.

EXCLUSION CRITERIA:

Excluded from the University of Pennsylvania study are those who have severe diseases that
involve myopia, such as Stickler s or Marfan syndromes, ocular disease such as Retinitis
Pigmentosa, and those with diseases that may secondarily cause myopia such as diabetes or
retinopathy of prematurity. Records of eye examinations obtained prior to the onset of
systemic or ocular disease will be accepted.

Individuals who complete the Risk Factor Questionnaire and who state that they were born
more than a month prematurely will not be included in the study.

Individuals who are myopic in one eye and unaffected in the other (ulnilateral myopes) will
not be included in the study.

Individuals who do not sign the Consent Form will be excluded, and families for whom all
necessary members do not sign the Consent Form will be excluded.

No fetuses, pregnant women, prisoners or other institutionalized individuals will be
enrolled.

Generally, myopia itself is not associated with mental impairment, although careful
consideration will be given to determining the cognitive understanding of any such
potentially impaired person appropriate for enrollment in order to assure that protection
of human rights is optimized.