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Editors Selection IGR 11-2
Genetic Variants of Glaucoma
Comment by Subhabrata Chakrabarti on:
21568 Association between MYOC.mt1 promoter polymorphism and risk of primary open-angle glaucoma: A systematic review and meta-analysis, Liu T; Zeng D; Zeng C et al., Medical Science Monitor, 2008; 14: RA87-RA93
Liu et al. (967) attempted to understand the role of a genetic variant in the promoter region of the myocilin gene, which is linked to POAG. This variant (MYOC.mt1) has been reported to be associated in some studies, while it was inconclusive in others. The authors performed a meta-analysis of four studies comprising of 835 cases and 530 controls that screened this variant. While they have tried to provide an understanding on the potential involvement of this variant in POAG, their rationale behind performing a meta-analysis lacks clarity. The main concern arises from the fact that genetic association studies based on case-control designs require a greater degree of validation both at the level of phenotype assessment and genotype screening. The authors have highlighted the lacunae in these studies in terms of similar clinical assessment and screening techniques. But they did not calculate the power and more importantly the effect size of the associated allele followed by the required sample size in these studies to demonstrate a significant association. With these two parameters, they could have easily demonstrated the reason for inconsistent associations.
Association of a single gene variant should be taken with a pinch of salt, unless the data are supported with a rigorous statistical analysis demonstrating a specific allele within a haplotype after multiple correctionsAssociation of a specific allele to a phenotype is usually inconclusive when it is based on a single variant (which could be by chance alone), but confirmative when they are based on a sequence of variants contributing to a risk haplotype (which is a function of the linkage disequilibrium between the variants). Recent studies on the AMDassociated genes such as CFH and ARMS2 have convincingly demonstrated these issues across different populations. Thus, association of a single gene variant should be taken with a pinch of salt, unless the data are supported with a rigorous statistical analysis demonstrating a specific allele within a haplotype after multiple corrections. Unfortunately, none of these issues have been addressed in this study.
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