April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Heritable High-grade Myopia: Fine-mapping Of The High-grade Myopia 3 Locus
Author Affiliations & Notes
  • Felicia Hawthorne
    Univ. Program in Genetics and Genomics,
    Center for Human Genetics,
    Duke University, Durham, North Carolina
  • Dianna Abbott
    Center for Human Genetics,
    Duke University, Durham, North Carolina
  • Khanh-Nhat Tran Viet
    Center for Human Genetics,
    Duke University, Durham, North Carolina
  • Ravikanth Metlapally
    Center for Human Genetics,
    Eye Center,
    Duke University, Durham, North Carolina
  • Janeen Morgan
    Center for Human Genetics,
    Duke University, Durham, North Carolina
  • Yi-Ju Li
    Center for Human Genetics,
    Duke University, Durham, North Carolina
  • Terri L. Young
    Center for Human Genetics,
    Eye Center,
    Duke University, Durham, North Carolina
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3294. doi:
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      Felicia Hawthorne, Dianna Abbott, Khanh-Nhat Tran Viet, Ravikanth Metlapally, Janeen Morgan, Yi-Ju Li, Terri L. Young; Heritable High-grade Myopia: Fine-mapping Of The High-grade Myopia 3 Locus. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3294.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To perform a high-density single nucleotide polymorphism (SNP) fine-mapping association study of the replicated, qualitatively assessed autosomal dominant high-grade myopia locus, MYP3 at chromosome 12q21-23 in a large family-based cohort

Methods: : Illumina Custom Goldengate genotyping of 768 selected interval SNPs was performed in 644 samples from 82 families with heritable high-grade myopia. Association analyses were performed for the qualitative trait of high myopia (SE < -6.00D) using the Pedigree Disequilibrium Test (PDT), and the Association in the Presence of Linkage (APL) test. In addition, the Quantitative Transmission Disequilibrium Test (QTDT) was conducted by treating refractive errors as quantitative traits. Quantitative tests were run for both dioptric sphere (SPH) and spherical equivalent (SE) phenotypes using both the average (avg) and the least (best) myopic of the two eyes.

Results: : Two contracted, strong association signals within MYP3 were found in all three tests; one at 78 Mb and the other at 96 Mb. The most significant markers did not overlap, however, clusters of significant markers were found in proximity. Significant results at 78 Mb were noted by PDT for RS10861796 (p = 0.0086) and APL for RS12301103 (p = 0.0057). At 96 Mb, the most significant p-value for PDT and APL was at RS7137537 (PDT p = 0.0111; APL p = 0.0016).For QTDT, the most significantly associated marker for all four traits at 78 Mb was RS4439580 (avg SPH p = 0.0014; avg SE p = 0.0002; best SPH p = 0.0038; best SE p = 0.0109). At 96 Mb, the most significantly associated marker was RS7953575 (avg SPH p = 0.0068; avg SE p = 0.0026; best SPH p = 0.0108; best SE p = 0.0018). The best p-value in this region was for avg SE at RS1971036 (p = 2X10-5).

Conclusions: : Significant SNP association signals were found in two distinct, contracted intervals within the MYP3 locus, supported by both qualitative and quantitative trait analyses. Chromosome 12 at 78 Mb and at 96 Mb may each contain causative or susceptibility genes for high myopia. Additional studies are underway to refine the association results and screen candidate genes within the intervals.

Keywords: myopia • genetics • gene mapping 
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