title: Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort.
abstract: OBJECTIVE
  Evidence from human myopia genetic mapping studies (MYP3 locus), modulated animal models, and observations of glycemic control in humans suggests that insulin-like growth factor (IGF)-1 plays a role in the control of eye growth. This study was conducted to determine whether IGF-1 polymorphisms are associated with myopia in a large, international dataset of Caucasian high-grade myopia pedigrees.
  
  
  METHODS
  Two hundred sixty-five multiplex families with 1391 subjects participated in the study. IGF-1 genotyping was performed with 13 selected tag single nucleotide polymorphisms (SNPs) using allelic discrimination assays. A family-based pedigree disequilibrium test (PDT) was performed to test for association. Myopia status was defined using sphere (SPH) or spherical equivalent (SE), and analyses assessed the association of (1) high-grade myopia (<or=-5.00 D), and (2) any myopia (<or=-0.50 D) with IGF-1 markers. Results were declared significant at P<or=0.0038 after Bonferroni correction. Q values that take into account multiple testing were also obtained.
  
  
  RESULTS
  In all, three SNPs-rs10860860, rs2946834, and rs6214-were present at P<0.05. SNP rs6214 showed positive association with both the high-grade- and any-myopia groups (P=2x10(-3) and P=2x10(-3), respectively) after correction for multiple testing.
  
  
  CONCLUSIONS
  The study supports a genetic association between IGF-1 and high-grade myopia. These findings are in line with recent evidence in an experimental myopia model showing that IGF-1 promotes ocular growth and axial myopia. IGF-1 may be a myopia candidate gene for further investigation.
authors.affiliation: Center for Human GeneticsDepartment of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Ravikanth
authors.initials: R
authors.lastname: Metlapally
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Khanh-Nhat
authors.initials: KN
authors.lastname: Tran-Viet
authors.forename: Diana
authors.initials: D
authors.lastname: Abbott
authors.forename: Francois
authors.initials: F
authors.lastname: Malecaze
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.forename: Sandrine
authors.initials: S
authors.lastname: Paget
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Guggenheim
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D038622:Internationality; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009216:Myopia / Q000208:ethnology* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D007334:Insulin-Like Growth Factor I