Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2.

Published online

Journal Article

PURPOSE: Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21-23 by four independent linkage studies. METHODS: We performed a genetic association study of the MYP3 locus in a family-based high-grade myopia cohort (n = 82) by genotyping 768 single-nucleotide polymorphisms (SNPs) within the linkage region. Qualitative testing for high-grade myopia (sphere ≤ -5 D affected, > -0.5 D unaffected) and quantitative testing on the average dioptric sphere were performed. RESULTS: Several genetic markers were nominally significantly associated with high-grade myopia in qualitative testing, including rs3803036, a missense mutation in PTPRR (P = 9.1 × 10(-4)) and rs4764971, an intronic SNP in UHRF1BP1L (P = 6.1 × 10(-4)). Quantitative testing determined statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10(-6)); rs7134216, in the 3' untranslated region (UTR) of DEPDC4 (P = 5.4 × 10(-7)); and rs17306116, an intronic SNP within PPFIA2 (P < 9 × 10(-4)). Independently conducted whole genome expression array analyses identified protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR). CONCLUSIONS: In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs4764971, was validated for quantitative association, and SNPs within PTPRR (quantitative) and PPFIA2 (qualitative and quantitative) approached significance. Three genes identified by our association study and supported by ocular expression and/or replication, UHRF1BP1L, PTPRR, and PPFIA2, are novel candidates for myopic development within the MYP3 locus that should be further studied.

Full Text

Duke Authors

Cited Authors

  • Hawthorne, F; Feng, S; Metlapally, R; Li, Y-J; Tran-Viet, K-N; Guggenheim, JA; Malecaze, F; Calvas, P; Rosenberg, T; Mackey, DA; Venturini, C; Hysi, PG; Hammond, CJ; Young, TL

Published Date

  • March 21, 2013

Published In

Volume / Issue

  • 54 / 3

Start / End Page

  • 2076 - 2086

PubMed ID

  • 23422819

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

Digital Object Identifier (DOI)

  • 10.1167/iovs.12-11102

Language

  • eng

Conference Location

  • United States