http://hdl.handle.net/10397/4707 Search the Channel search http://repository.lib.polyu.edu.hk/jspui/simple-search http://hdl.handle.net/10397/5806 Title: Linkage and association of myocilin (MYOC) polymorphisms with high myopia in a Chinese population<br/><br/>Authors: Tang, Wing Chun; Yip, Shea-ping; Lo, Ka Kin; Ng, Po Wah; Choi, Pik Shan; Lee, Sau Yin; Yap, Keng-hung Maurice<br/><br/>Abstract: Purpose: 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. Wed, 04 Apr 2007 00:00:00 GMT http://hdl.handle.net/10397/5162 Title: Evaluation of proteoglycan gene polymorphisms as risk factors in the genetic susceptibility to high myopia<br/><br/>Authors: Yip, Shea-ping; Leung, Kim-hung; Ng, Po Wah; Fung, Wai Yan; Sham, Pak Chung; Yap, Keng-hung Maurice<br/><br/>Abstract: Purpose. To investigate the relationship between high myopia and single nucleotide polymorphisms (SNPs) in six proteoglycan genes: aggrecan (ACAN), fibromodulin (FMOD), decorin (DCN), lumican (LUM), keratocan (KERA), and epiphycan (EPYC). These genes were selected for study because they are involved in induced myopia in animals and/or are within the human MYP3 locus identified by linkage analysis of families with high myopia.; Methods. Two groups of Chinese subjects were studied: group 1 (300 cases and 300 controls) and group 2 (356 cases and 354 controls). Cases were high myopes with spherical equivalent (SE) ≤ −8.00 D, and controls had SE between +1.0 and −1.0 D. From these candidate genes, 60 tagging SNPs were selected. First, 12 DNA pools were each constructed from 50 samples of the same phenotype from group 1 subjects and were tested for association with the SNPs. Second, putatively positive SNPs were confirmed by individual genotyping of group 1 subjects. Finally, positive results were replicated in group 2 subjects.; Results. Of the 58 SNPs successfully screened by DNA pooling, 8 ACAN SNPs passed the threshold of P ≤ 0.10 (nested ANOVA) and were then genotyped in the individual samples. Haplotypes rs3784757 and rs1516794 showed significant association with high myopia. However, the positive result could not be replicated in the second subject group.; Conclusions. These six proteoglycan genes were not associated with high myopia in these Chinese subjects and hence are unlikely to be important in the genetic predisposition to high myopia.<br/><br/>Description: DOI: 10.1167/iovs.11-7639 Tue, 16 Aug 2011 00:00:00 GMT http://hdl.handle.net/10397/5161 Title: Association of high myopia with crystallin beta A4 (CRYBA4) gene polymorphisms in the linkage-identified MYP6 locus<br/><br/>Authors: Ho, Daniel W. H.; Yap, Keng-hung Maurice; Ng, Po Wah; Fung, Wai Yan; Yip, Shea-ping<br/><br/>Abstract: Background: Myopia is the most common ocular disorder worldwide and imposes tremendous burden on the society. It is a complex disease. The MYP6 locus at 22 q12 is of particular interest because many studies have detected linkage signals at this interval. The MYP6 locus is likely to contain susceptibility gene(s) for myopia, but none has yet been identified.; Methodology/Principal Findings: Two independent subject groups of southern Chinese in Hong Kong participated in the study an initial study using a discovery sample set of 342 cases and 342 controls, and a follow-up study using a replication sample set of 316 cases and 313 controls. Cases with high myopia were defined by spherical equivalent # -8 dioptres and emmetropic controls by spherical equivalent within 61.00 dioptre for both eyes. Manual candidate gene selection from the MYP6 locus was supported by objective in silico prioritization. DNA samples of discovery sample set were genotyped for 178 tagging single nucleotide polymorphisms (SNPs) from 26 genes. For replication, 25 SNPs (tagging or located at predicted transcription factor or microRNA binding sites) from 4 genes were subsequently examined using the replication sample set. Fisher P value was calculated for all SNPs and overall association results were summarized by meta-analysis. Based on initial and replication studies, rs2009066 located in the crystallin beta A4 (CRYBA4) gene was identified to be the most significantly associated with high myopia (initial study: P = 0.02; replication study: P = 1.88e-4; meta-analysis: P = 1.54e-5) among all the SNPs tested. The association result survived correction for multiple comparisons. Under the allelic genetic model for the combined sample set, the odds ratio of the minor allele G was 1.41 (95% confidence intervals, 1.21-1.64).; Conclusions/Significance: A novel susceptibility gene (CRYBA4) was discovered for high myopia. Our study also signified the potential importance of appropriate gene prioritization in candidate selection.<br/><br/>Description: DOI: 10.1371/journal.pone.0040238 Fri, 29 Jun 2012 00:00:00 GMT http://hdl.handle.net/10397/5160 Title: Genotyping performance assessment of whole genome amplified DNA with respect to multiplexing level of assay and its period of storage<br/><br/>Authors: Ho, Daniel W. H.; Yiu, Wai Chi; Yap, Keng-hung Maurice; Fung, Wai Yan; Ng, Po Wah; Yip, Shea-ping<br/><br/>Abstract: Whole genome amplification can faithfully amplify genomic DNA (gDNA) with minimal bias and substantial genome coverage. Whole genome amplified DNA (wgaDNA) has been tested to be workable for high-throughput genotyping arrays. However, issues about whether wgaDNA would decrease genotyping performance at increasing multiplexing levels and whether the storage period of wgaDNA would reduce genotyping performance have not been examined. Using the Sequenom MassARRAY iPLEX Gold assays, we investigated 174 single nucleotide polymorphisms for 3 groups of matched samples: group 1 of 20 gDNA samples, group 2 of 20 freshly prepared wgaDNA samples, and group 3 of 20 stored wgaDNA samples that had been kept frozen at −70°C for 18 months. MassARRAY is a medium-throughput genotyping platform with reaction chemistry different from those of high-throughput genotyping arrays. The results showed that genotyping performance (efficiency and accuracy) of freshly prepared wgaDNA was similar to that of gDNA at various multiplexing levels (17-plex, 21-plex, 28-plex and 36-plex) of the MassARRAY assays. However, compared with gDNA or freshly prepared wgaDNA, stored wgaDNA was found to give diminished genotyping performance (efficiency and accuracy) due to potentially inferior quality. Consequently, no matter whether gDNA or wgaDNA was used, better genotyping efficiency would tend to have better genotyping accuracy.<br/><br/>Description: DOI: 10.1371/journal.pone.0026119 Tue, 11 Oct 2011 00:00:00 GMT