High myopia is not associated with the SNPs in the TGIF, lumican, TGFB1, and HGF genes.

PURPOSE Four single-nucleotide polymorphisms (SNPs) in the TGIF, lumican, TGFB1, and HGF genes have been declared to be associated with high myopia in Chinese living in southeast China, but none of them has been confirmed by additional studies. This study was conducted to verify the reported positive association results by analysis of subjects from the same region. METHODS DNA was prepared from venous leukocytes of 288 patients with high myopia and 208 control subjects. The four SNPs (rs2229336, rs3759223, rs1982073, and rs3735520) in the four genes were genotyped by restriction fragment length polymorphism (RFLP) analysis. The allele and genotype frequencies of these SNPs from patients and control subjects were compared by chi(2) test. RESULTS Polymorphism at rs2229336 was not detected in all 496 subjects. There were no statistically significant differences between patients and control subjects for the other three SNPs: rs3759223, rs1982073, and rs3735520. CONCLUSIONS The study does not support the association of high myopia with alleles of rs2229336 in TGIF, rs3759223 in lumican, rs1982073 in TGFB1, and rs3735520 in HGF. These results provide a view contrary to those in previous reports. Reasonable criteria as well as replication should be the first priority for genetic association studies to avoid excessive expansion of false-positive results, especially for high myopia.

[1]  M. McCarthy,et al.  Genome-wide association studies for complex traits: consensus, uncertainty and challenges , 2008, Nature Reviews Genetics.

[2]  F. Dudbridge,et al.  Estimation of significance thresholds for genomewide association scans , 2008, Genetic epidemiology.

[3]  M. McCarthy,et al.  Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes , 2008, Nature Genetics.

[4]  John R Thompson,et al.  Biostatistical Aspects of Genome‐Wide Association Studies , 2008, Biometrical journal. Biometrische Zeitschrift.

[5]  Mark M Iles,et al.  What Can Genome-Wide Association Studies Tell Us about the Genetics of Common Disease , 2008, PLoS genetics.

[6]  C. Hammond,et al.  Comment on ‘A PAX6 gene polymorphism is associated with genetic predisposition to extreme myopia’ , 2008, Eye.

[7]  S. Yip,et al.  A review of current approaches to identifying human genes involved in myopia , 2008, Clinical & experimental optometry.

[8]  C. Gieger,et al.  Genomewide association analysis of coronary artery disease. , 2007, The New England journal of medicine.

[9]  Joseph T. Glessner,et al.  A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene , 2007, Nature.

[10]  D. Gudbjartsson,et al.  Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes , 2007, Nature Genetics.

[11]  Gonçalo R. Abecasis,et al.  Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma , 2007, Nature.

[12]  Alastair Forbes,et al.  Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility , 2007, Nature Genetics.

[13]  D. Gudbjartsson,et al.  Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor–positive breast cancer , 2007, Nature Genetics.

[14]  Lester L. Peters,et al.  Genome-wide association study identifies novel breast cancer susceptibility loci , 2007, Nature.

[15]  A. Gylfason,et al.  A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction , 2007, Science.

[16]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[17]  H. Inoko,et al.  Exclusion of Transforming Growth Factor-b1 as a Candidate Gene for Myopia in the Japanese , 2007, Japanese Journal of Ophthalmology.

[18]  S. Yip,et al.  Linkage and association of myocilin (MYOC) polymorphisms with high myopia in a Chinese population , 2007, Molecular vision.

[19]  Simon Heath,et al.  Novel Crohn Disease Locus Identified by Genome-Wide Association Maps to a Gene Desert on 5p13.1 and Modulates Expression of PTGER4 , 2007, PLoS genetics.

[20]  T. Hudson,et al.  A genome-wide association study identifies novel risk loci for type 2 diabetes , 2007, Nature.

[21]  S. Juo,et al.  Systematic assessment of the tagging polymorphisms of the COL1A1 gene for high myopia , 2007, Journal of Human Genetics.

[22]  Xueshan Xiao,et al.  The 208delG mutation in FSCN2 does not associate with retinal degeneration in Chinese individuals. , 2007, Investigative ophthalmology & visual science.

[23]  M. Khoury,et al.  Most Published Research Findings Are False—But a Little Replication Goes a Long Way , 2007, PLoS medicine.

[24]  C. Haley,et al.  Correlations in refractive errors between siblings in the Singapore Cohort Study of Risk factors for Myopia , 2006, British Journal of Ophthalmology.

[25]  Jerzy K. Kulski,et al.  Analysis of single nucleotide polymorphisms at 13 loci within the transforming growth factor-induced factor gene shows no association with high myopia in Japanese subjects , 2006, Immunogenetics.

[26]  D. Balding.  A tutorial on statistical methods for population association studies , 2006, Nature Reviews Genetics.

[27]  S. Baudouin,et al.  A systematic review of the quality of genetic association studies in human sepsis , 2006, Intensive Care Medicine.

[28]  C. K. Hsiao,et al.  The association of single nucleotide polymorphisms in the 5'-regulatory region of the lumican gene with susceptibility to high myopia in Taiwan. , 2006, Molecular vision.

[29]  F. Tsai,et al.  The TGFbeta1 gene codon 10 polymorphism contributes to the genetic predisposition to high myopia. , 2006, Molecular vision.

[30]  S. Yip,et al.  Family-based association analysis of hepatocyte growth factor (HGF) gene polymorphisms in high myopia. , 2006, Investigative ophthalmology & visual science.

[31]  D. Wotton,et al.  TGIF Inhibits Retinoid Signaling , 2006, Molecular and Cellular Biology.

[32]  Suzanne M Leal,et al.  Detection of genotyping errors and pseudo‐SNPs via deviations from Hardy‐Weinberg equilibrium , 2005, Genetic epidemiology.

[33]  J. Hejtmancik,et al.  Novel locus for X linked recessive high myopia maps to Xq23–q25 but outside MYP1 , 2005, Journal of Medical Genetics.

[34]  Kenneth F. Manly,et al.  Reliability of statistical associations between genes and disease , 2005, Immunogenetics.

[35]  J. Hejtmancik,et al.  A new locus for autosomal dominant high myopia maps to 4q22-q27 between D4S1578 and D4S1612. , 2005, Molecular vision.

[36]  E. Rappaport,et al.  Identification of a novel locus on 2q for autosomal dominant high-grade myopia. , 2005, Investigative ophthalmology & visual science.

[37]  J. Hirschhorn,et al.  Genetic association studies of complex traits: design and analysis issues. , 2005, Mutation research.

[38]  J. Matsubara,et al.  Stage specificity of novel growth factor expression during development of proliferative vitreoretinopathy , 2005, Eye.

[39]  J. Gilbert,et al.  Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration , 2005, Science.

[40]  A. Edwards,et al.  Complement Factor H Polymorphism and Age-Related Macular Degeneration , 2005, Science.

[41]  J. Ott,et al.  Complement Factor H Polymorphism in Age-Related Macular Degeneration , 2005, Science.

[42]  M. Daly,et al.  Genome-wide association studies for common diseases and complex traits , 2005, Nature Reviews Genetics.

[43]  D. Goldstein,et al.  Association of genetic loci: Replication or not, that is the question , 2004, Neurology.

[44]  T. Young,et al.  Sequence variants in the transforming growth beta-induced factor (TGIF) gene are not associated with high myopia. , 2004, Investigative ophthalmology & visual science.

[45]  T. Young,et al.  Exclusion of lumican and fibromodulin as candidate genes in MYP3 linked high grade myopia. , 2004, Molecular vision.

[46]  N. Mcbrien,et al.  Isoform-specific Changes in Scleral Transforming Growth Factor-β Expression and the Regulation of Collagen Synthesis during Myopia Progression* , 2004, Journal of Biological Chemistry.

[47]  S. Chew,et al.  Prevalence, incidence, and progression of myopia of school children in Hong Kong. , 2004, Investigative ophthalmology & visual science.

[48]  Wei Li,et al.  [The SNPs analysis of encoding sequence of interacting factor gene in Chinese population]. , 2003, Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics.

[49]  Robert W. Williams,et al.  Molecular biology of myopia § , 2003, Clinical & experimental optometry.

[50]  F. Schaeffel,et al.  Interactions of genes and environment in myopia. , 2003, Developments in ophthalmology.

[51]  A. Oldberg,et al.  Ocular and scleral alterations in gene-targeted lumican-fibromodulin double-null mice. , 2003, Investigative ophthalmology & visual science.

[52]  V. Choo.  A look at slowing progression of myopia , 2003, The Lancet.

[53]  O. Mäkitie,et al.  New locus for autosomal dominant high myopia maps to the long arm of chromosome 17. , 2003, Investigative ophthalmology & visual science.

[54]  K. Ogawa,et al.  Regulation of TG-interacting factor by transforming growth factor-beta. , 2003, The Biochemical journal.

[55]  P. McKeigue,et al.  Problems of reporting genetic associations with complex outcomes , 2003, The Lancet.

[56]  Y. Leung,et al.  TGFβ-Induced Factor: A Candidate Gene for High Myopia , 2003 .

[57]  Jianfeng Xu,et al.  Positive results in association studies are associated with departure from Hardy-Weinberg equilibrium: hint for genotyping error? , 2002, Human Genetics.

[58]  B. A. Austin,et al.  Altered collagen fibril formation in the sclera of lumican-deficient mice. , 2002, Investigative ophthalmology & visual science.

[59]  J. Hirschhorn,et al.  A comprehensive review of genetic association studies , 2002, Genetics in Medicine.

[60]  John A. Todd,et al.  Parameters for reliable results in genetic association studies in common disease , 2002, Nature Genetics.

[61]  O. Rascol,et al.  A genome wide scan for familial high myopia suggests a novel locus on chromosome 7q36 , 2002, Journal of medical genetics.

[62]  L. Palmer,et al.  Genomewide scans of complex human diseases: true linkage is hard to find. , 2001, American journal of human genetics.

[63]  L. Atwood,et al.  Further refinement of the MYP2 locus for autosomal dominant high myopia by linkage disequilibrium analysis , 2001, Ophthalmic genetics.

[64]  Michael Krawczak,et al.  Genetic association studies of bronchial asthma – a need for Bonferroni correction? , 2000, Human Genetics.

[65]  H. Taylor,et al.  Myopia and vision 2020. , 2000, American journal of ophthalmology.

[66]  C. Sotozono,et al.  Growth factors: importance in wound healing and maintenance of transparency of the cornea , 2000, Progress in Retinal and Eye Research.

[67]  R. Pararajasegaram.  VISION 2020-the right to sight: from strategies to action. , 1999, American journal of ophthalmology.

[68]  W S Oetting,et al.  A second locus for familial high myopia maps to chromosome 12q. , 1998, American journal of human genetics.

[69]  C. Birchmeier,et al.  Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. , 1998, Trends in cell biology.

[70]  L. Atwood,et al.  Evidence that a locus for familial high myopia maps to chromosome 18p. , 1998, American journal of human genetics.

[71]  E. Lander,et al.  Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results , 1995, Nature Genetics.

[72]  M. Haim,et al.  X‐linked myopia: Bornholm Eye Disease , 1990, Clinical genetics.

[73]  P. Mitchell,et al.  Assessment of TGIF as a candidate gene for myopia. , 2008, Investigative ophthalmology & visual science.

[74]  J. Brooks.  Why most published research findings are false: Ioannidis JP, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece , 2008 .

[75]  稲森 由美子.  The COL1A1 gene and high myopia susceptibility in Japanese , 2008 .

[76]  R. Metlapally,et al.  Complex trait genetics of refractive error. , 2007, Archives of ophthalmology.

[77]  蔡長海,et al.  The TGFbeta1 gene codon 10 polymorphism contributes to the genetic predisposition to high myopia. , 2006 .

[78]  J. Ott.  Association of genetic loci: replication or not, that is the question. , 2004, Neurology.

[79]  Y. Leung,et al.  TGFbeta-induced factor: a candidate gene for high myopia. , 2003, Investigative ophthalmology & visual science.

[80]  David M. Evans,et al.  Genome-wide association analysis identifies 20 loci that influence adult height , 2008, Nature Genetics.