title: Linkage and association of myocilin (MYOC) polymorphisms with high myopia in a Chinese population.
abstract: OBJECTIVE
  To test the association between myocilin gene (MYOC) polymorphisms and high myopia in Hong Kong Chinese by using family-based association study.
  
  
  METHODS
  A total of 162 Chinese nuclear families, consisting of 557 members, were recruited from an optometry clinic. Each family had two parents and at least one offspring with high myopia (defined as -6.00D or less for both eyes). All offspring were healthy with no clinical evidence of syndromic disease and other ocular abnormality. Genotyping was performed for two MYOC microsatellites (NGA17 and NGA19) and five tag single nucleotide polymorphisms (SNPs) spreading across the gene. The genotype data were analyzed with Family-Based Association Test (FBAT) software to check linkage and association between the genetic markers and myopia, and with GenAssoc to generate case and pseudocontrol subjects for investigating main effects of genetic markers and calculating the genotype relative risks (GRR).
  
  
  RESULTS
  FBAT analysis showed linkage and association with high myopia for two microsatellites and two SNPs under one to three genetic models after correction for multiple comparisons by false discovery rate. NGA17 at the promoter was significant under an additive model (p=0.0084), while NGA19 at the 3' flanking region showed significant results under both additive (p=0.0172) and dominant (p=0.0053) models. SNP rs2421853 (C>T) exhibited both linkage and association under additive (p=0.0009) and dominant/recessive (p=0.0041) models. SNP rs235858 (T>C) was also significant under additive (p=4.0E-6) and dominant/recessive (p=2.5E-5) models. Both SNPs were downstream of NGA19 at the 3' flanking region. Positive results for these SNPs were novel findings. A stepwise conditional logistic regression analysis of the case-pseudocontrol dataset generated by GenAssoc from the families showed that both SNPs could separately account for the association of NGA17 or NGA19, and that both SNPs contributed separate main effects to high myopia. For rs2421853 and with C/C as the reference genotype, the GRR increased from 1.678 for G/A to 2.738 for A/A (p=9.0E-4, global Wald test). For rs235858 and with G/G as the reference, the GRR increased 2.083 for G/A to 3.931 for A/A (p=2.0E-2, global Wald test). GRR estimates thus suggested an additive model for both SNPs, which was consistent with the finding that, of the three models tested, the additive model gave the lowest p values in FBAT analysis.
  
  
  CONCLUSIONS
  Linkage and association was shown between the MYOC polymorphisms and high myopia in our family-based association study. The SNP rs235858 at the 3' flanking region showed the highest degree of confidence for association.
authors: School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
authors: Wing Chun
authors: WC
authors: Tang
authors: Shea Ping
authors: SP
authors: Yip
authors: Ka Kin
authors: KK
authors: Lo
authors: Po Wah
authors: PW
authors: Ng
authors: Pik Shan
authors: PS
authors: Choi
authors: Sau Yin
authors: SY
authors: Lee
authors: Maurice K H
authors: MK
authors: Yap
mesh_terms: D024509:3' Flanking Region; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009216:Myopia / Q000235:genetics / Q000503:physiopathology*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D012720:Severity of Illness Index; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D005819:Genetic Markers; D006023:Glycoproteins; D000099179:Myocilin