title: Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2.
abstract: OBJECTIVE
  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.
authors: Duke Center for Human Genetics, Duke University, Durham, NC 27710, USA.
authors: Felicia
authors: F
authors: Hawthorne
authors: Sheng
authors: S
authors: Feng
authors: Ravikanth
authors: R
authors: Metlapally
authors: Yi-Ju
authors: YJ
authors: Li
authors: Khanh-Nhat
authors: KN
authors: Tran-Viet
authors: Jeremy A
authors: JA
authors: Guggenheim
authors: Francois
authors: F
authors: Malecaze
authors: Patrick
authors: P
authors: Calvas
authors: Thomas
authors: T
authors: Rosenberg
authors: David A
authors: DA
authors: Mackey
authors: Cristina
authors: C
authors: Venturini
authors: Pirro G
authors: PG
authors: Hysi
authors: Christopher J
authors: CJ
authors: Hammond
authors: Terri L
authors: TL
authors: Young
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009216:Myopia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7 / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C470384:PPFIA2 protein, human; C581175:UHRF1BP1L protein, human; C513469:PTPRR protein, human; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7