A common genetic variant as an effect modifier for primary angle closure glaucoma.

Area of Science:

• Ophthalmology
• Genetics
• Epidemiology

Background:

• Primary angle closure glaucoma (PACG) has a known genetic component.
• Genome-wide association studies (GWAS) have identified potential susceptibility genes.
• The role of the COL11A1 gene variant rs3753841 in PACG requires further clarification due to conflicting previous findings.

Purpose of the Study:

• To conduct a meta-analysis to determine the association between the COL11A1 gene variant rs3753841 and PACG.
• To clarify the elusive role of this specific genetic variant in PACG development.

Main Methods:

• Systematic computer-based searches were performed to identify relevant studies.
• Two investigators selected eligible studies based on predefined inclusion criteria.
• Pooled odds ratios were estimated using the DerSimonian and Laird method under various genetic models, with heterogeneity assessed using the chi-square Q statistic and I(2) metric.

Main Results:

• A significant association was found between the COL11A1 rs3753841 variant and PACG in 26,365 subjects (5,594 cases, 20,771 controls) of Asian and Caucasian ancestry across 15 studies.
• The association was stronger in individuals with the GG genotype (GG vs AA: OR 1.26; GG vs GA + AA: OR 1.24).
• Statistical significance was maintained in stratified analyses for Asian populations and studies deviating from Hardy-Weinberg equilibrium.

Conclusions:

• The COL11A1 rs3753841 variant may increase susceptibility to PACG.
• This large-scale meta-analysis provides valuable insights into the genetic underpinnings of PACG, the most common glaucoma subtype.