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Originally published In Press as doi:10.1167/iovs.08-2848 on January 17, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:2024-2032.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2848
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Genomewide Linkage Scans for Ocular Refraction and Meta-analysis of Four Populations in the Myopia Family Study

Robert Wojciechowski,1 Dwight Stambolian,2,3 Elise Ciner,4 Grace Ibay,1 Taura N. Holmes,1 and Joan E. Bailey-Wilson1

1From the Inherited Disease Research Branch, National Human Genome Research Institute (NIH), Baltimore, Maryland; the 2Departments of Ophthalmology and 3Genetics, University of Pennsylvania, Philadelphia, Pennsylvania; and 4The Eye Institute of the Pennsylvania College of Optometry, Philadelphia, Pennsylvania.

PURPOSE. Genomewide linkage scans were performed in Caucasian (CAUC) and Old Order Amish (OOA) families to identify genomic regions containing genes responsible for refractive error control. We also performed a meta-analysis by combining these results with our previous linkage results from Ashkenazi Jewish (ASHK) and African American (AFRAM) families.

METHODS. Two hundred seventy-one CAUC and 411 OOA participants (36 and 61 families, respectively) were recruited to participate in the Myopia Family Study. Recruitment criteria were designed to enrich the sample for multiplex myopic families. Genomewide, model-free, multipoint linkage analyses were performed separately for each population by using >370 microsatellite markers. Empirical significance levels were determined via gene-dropping simulations. A meta-analysis was performed by combining linkage results from the CAUC, OOA, AFRAM, and ASHK samples, and results were compared to previously reported loci for myopia and refraction.

RESULTS. Suggestive evidence of linkage was found at 12q24 (LOD = 4.583, P = 0.00037) and 4q21 (LOD = 2.72, P = 0.0028) in the CAUC sample and at 5qter (LOD = 3.271, P = 0.0014) in the OOA. Meta-analysis linkage results were largely driven by population-specific signals from ASHK and AFRAM families. The meta-analysis showed suggestive evidence of linkage to 4q21-22 (meta-P = 0.00214) adjacent to the previously reported MYP9 and MYP11 loci.

CONCLUSIONS. The results showed suggestive evidence of linkage of ocular refraction to 12q24 and 4q21 in CAUC and to 5qter in OOA families. The meta-analysis supports the view that several genes play a role in refractive development across populations. In MFS families, four broad genomic regions (on 1p, 4q, 7p, and 12q) most likely contain genes that influence ocular refraction.






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