Association of GJD2 polymorphisms with myopia: a systematic review and meta-analysis

Abstract Polymorphisms in the gap junction protein delta 2 ( GJD2 ) gene have been associated with myopia, but findings across individual studies have been inconsistent. This study aimed to systematically update and synthesize the available evidence regarding the association between GJD2 variants and myopia susceptibility. A systematic literature search was conducted in PubMed, Cochrane Library, Embase and Web of Science. Case–control studies published in English with sufficient data to estimate odds ratios (ORs) and 95% confidence intervals (CIs) were included. Study quality and publication bias were evaluated using the Newcastle–Ottawa Scale (NOS) and funnel plots. Pooled ORs with 95% CIs were calculated using fixed- or random-effects models and displayed in forest plots. Heterogeneity was assessed with the Cochrane Q test and I 2 statistic. Sixteen studies were included in qualitative synthesis, and nine comprising 9268 participants were eligible for meta-analysis. Significant associations were detected for rs634990 and rs524952 across multiple genetic models, although the evidence for rs634990 was less robust because of substantial between-study heterogeneity. For rs524952, carriers of the risk genotype had an increased likelihood of myopia (OR = 1.41, 95% CI 1.25–1.60) and high myopia (OR = 1.43, 95% CI 1.25–1.64). Sensitivity analyses excluding the study by Qiang et al., studies involving pathological myopia, and the only study using an axial length-based definition yielded comparable effect estimates, although heterogeneities remained for some genetic models. Evidence for rs651724 was limited, with only two studies available and no significant association detected. Funnel plots did not show obvious asymmetry, although publication bias could not be excluded because of the limited number of included studies. GJD2 polymorphisms, particularly rs524952, were associated with increased susceptibility to myopia and high myopia. Further studies in diverse populations and functional investigations are needed to further evaluate these associations and clarify their biological relevance to refractive development.