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

Not Applicable

Completed

• Conditions: Myopia
• Interventions: Genetic: blood sample

• Registration Number: NCT02583620
• Lead Sponsor: University Hospital, Toulouse

Brief 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.

Study Timeline

• Study Start: 2009-09
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Study First Submitted: 2015-08-18
• Status Verified: 2015-10
• Study First Submitted QC: 2015-10-20
• Last Update Submitted: 2015-10-20
• Study First Posted: 2015-10-22
• Last Update Posted: 2015-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 553

Inclusion Criteria

• high myopic (cases) volunteers,
• emmetropic (controls) volunteers

Exclusion Criteria

• syndromic myopic children under 18 years,
• non autonomous adults

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Emmetropic volunteers	blood sample	Blood sample
High myopic volunteers	blood sample	Blood sample

Primary Outcome Measures

Name	Time	Method
Numbers of allele frequencies at markers in the population	Baseline	Numbers of allele frequencies at markers in the population

Trial Locations

Locations (4)

CHU Bordeaux Hôpital Pellegrin; 🇫🇷 Bordeaux, France

CHU Pointe-à-Pitre; 🇫🇷 Pointe-à-Pitre, Guadeloupe, France

CHU Limoges Hôpital Dupuytren; 🇫🇷 Limoges, France

CHU Toulouse Hôpital Purpan; 🇫🇷 Toulouse, France