Identification of Genomic Loci Determining Susceptibility to the Development of High Myopia
Condition: Myopia
MeSH terms: Myopia
Study type: Interventional

Summary: 
      Compelling evidence of genetic components in high myopia has been put forward by several
      studies. Twin cohorts, familial linkage studies and population studies has described at least
      10 loci containing genes involved in the disease development. The investigators previously
      demonstrated novel linkage on chromosome 7q36 and chromosome 7p15 in French families. A new
      approach consisting of a case-control based population association study is underway in order
      to recover a high number of myopic subjects avoiding the limitation of familial cases. 1.8
      millions polymorphic markers will be compared with emmetropic controls in order to recover
      loci associated with the disease in the population.
    

Detailed description: 
      Myopia is a worldwide refractive ocular disorder and is the most frequent visual defect in
      man. It is responsible for a major health problem, affecting around 25% of the western
      population. High myopia is the most severe form of the myopic spectrum and is defined by an
      increase of refractive error beyond -5 dioptres. About 2.5% of the general population suffers
      from this, while the secondary complications are responsible among these patients for the 4th
      cause of legal blindness. The physiopathology of myopia remains unknown and mechanisms
      leading to the disease are most probably complex, mixing acquired environmental and genetics
      factors. Our team in a previous study gathered and analysed an important series of high
      myopic families: Heritability, segregation and linkage analyses modelling the transmission
      mode localised two major genomic regions linked to high myopia susceptibility on chromosome
      7q36 and chromosome 7p15. Several loci have been described by other teams working on the same
      topic among different human populations. Very recently reappraisal of 55 families led to the
      delineation of a complex segregation model of the high myopia phenotype thus claiming an
      oligo- polygenic mode of transmission. Together these results express the need to collect
      more cases and to substitute an linkage studies by association studies already conducted in
      order to increase the power to detect involved loci.

      To find one or more genomic loci involved in high myopia susceptibility; a polygenic model
      and association analysis is considered a referent method to decipher the participation of
      multiple, low acting loci. High density SNPs/CNVs DNA markers covering the whole genome will
      be used for genotyping.

      Phenotypes including ophthalmologic evaluation, ethno-geographic origin and familial data
      will be collected in order to allow further stratification or clustering.

      Computing of the statistical power of the association analysis conducted to minimize the
      number of false positive associations and to obtain a 80% of detection power indicated the
      need of 400 high myopic subjects and 400 controls to be analysed.

      Collaboration between a Clinical Investigation Center (CIC) and Ophthalmology clinics will be
      used to overcome recruitment problems. DNA extraction and genotyping will be conducted in
      Institut national de la santé et de la recherche (INSERM-UPS) unit in Toulouse using the
      "Toulouse's Génopole" microarrays genotyping facilities.
    

Intervention name(s): blood sample
Intervention type(s): Genetic
Intervention description(s): A blood test is realized on the subject
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: high myopia