Identification of Genomic Loci Determining Susceptibility to the Development of High Myopia

Myopia Clinical Trial

— ASSOMYP  

Official title:

Identification of Genomic Loci Determining Susceptibility to the Development of High Myopia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02583620
• Other study ID #: 09 036 08
• Status: Completed
• Phase: N/A
• First received: August 18, 2015
• Last updated: October 20, 2015
• Start date: September 2009
• Est. completion date: September 2014

Study information

• Verified date: October 2015
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 553
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• high myopic (cases) volunteers,

• emmetropic (controls) volunteers

Exclusion Criteria:

• syndromic myopic children under 18 years,

• non autonomous adults

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Disease Susceptibility
• Myopia

Intervention

Genetic:
• blood sample
A blood test is realized on the subject

Locations

Country	Name	City	State
France	CHU Bordeaux Hôpital Pellegrin	Bordeaux
France	CHU Limoges Hôpital Dupuytren	Limoges
France	CHU Pointe-à-Pitre	Pointe-à-Pitre	Guadeloupe
France	CHU Toulouse Hôpital Purpan	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numbers of allele frequencies at markers in the population	Numbers of allele frequencies at markers in the population	Baseline	No