July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Rare Variant TDT Association Study of Familial Myopia in Caucasian Families
Author Affiliations & Notes
  • Deyana Lewis
    Computational and Statistical Genomics Branch, National Human Genome Research Insitute , Baltimore, Maryland, United States
  • Claire L. Simpson
    Genetics, Genomics and Informatics, University of Tennessee Health Sciences Center, Memphis, Tennessee, United States
    Computational and Statistical Genomics Branch, National Human Genome Research Insitute , Baltimore, Maryland, United States
  • Anthony Musolf
    Computational and Statistical Genomics Branch, National Human Genome Research Insitute , Baltimore, Maryland, United States
  • Kyle Long
    University of Texas at El Paso, El Paso, Texas, United States
  • Laura Portas
    Institute of Population Genetics, Sassar, Italy
  • Federico Murgia
    Institute of Population Genetics, Sassar, Italy
  • Elise B. Ciner
    Ophthalmology, Salus University, Elkins Park, Pennsylvania, United States
  • Dwight Stambolian
    Ophthalmology, Perelman School of Medicine,University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Joan E Bailey-Wilson
    Computational and Statistical Genomics Branch, National Human Genome Research Insitute , Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Deyana Lewis, None; Claire Simpson, None; Anthony Musolf, None; Kyle Long, None; Laura Portas, None; Federico Murgia, None; Elise Ciner, None; Dwight Stambolian, None; Joan Bailey-Wilson, None
  • Footnotes
    Support  NEI Grant EY020483 and support from the Intramural Research Program of the National
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1825. doi:
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      Deyana Lewis, Claire L. Simpson, Anthony Musolf, Kyle Long, Laura Portas, Federico Murgia, Elise B. Ciner, Dwight Stambolian, Joan E Bailey-Wilson; Rare Variant TDT Association Study of Familial Myopia in Caucasian Families. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1825.

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

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Abstract

Purpose : Genome-wide association studies and linkage studies have identified loci influencing the risk of developing myopia but, few causal variants have been identified with the majority of them being common (minor allele frequency > 0.05). Therefore, this study aims to identify regions associated with rare variants that increase myopia risk using dense Exome Chip genotyping data from 75 myopic Caucasian families from the Penn Family Myopia Study.

Methods : 25 Myopic Caucasian parent-child trios (selected from multiplex families) were independently genotyped using the Illumina Human Exome v1.1 array plus. Myopia was defined based on mean spherical equivalent in Diopters (D): affected (≤-1D), unaffected (≥0 D) or unknown (<0D, >-1 D). After quality control, 27,121 SNPs were analyzed using a rare-variant transmission disequilibrium test (RV-TDT) to perform gene-based association tests with rare variants.

Results : RV-TDT analysis identified a suggestively associated locus on chromosome 2q31.1 for a non-synonymous coding SNP rs34564141 in the low density lipoprotein receptor-related protein 2 (LRP2) gene after correcting for multiple testing (P value = 2.65x10-3). LRP2 has been implicated in a study of a rare form of severe myopia in patients who had a mutation in the LRP2 gene, encoding a receptor LRP2 in the retina. Additionally, greatly enlarged eyes have been observed in mice lacking this LRP2 gene.

Conclusions :
No detected associations met exome wide significance or nominal significance of an α level of 0.05 Bonferroni corrected for 11,362 genes. We are extending these analyses to include 350 individuals from additional myopic family cohorts, including Ashkenazi Jewish , African American, and Chinese families which we will present these results.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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