۱- Background

۲- Methods

۳- Results

۴- Discussion

۵- Strengths and limitations

۶- Conclusion

۷- Search strategy and inclusion criteria

References

Abstract

We have systematically extracted all available heritability (h2) estimates of glaucoma and related endophenotypes from the literature and summarized the evidence by meta-analysis. Glaucoma endophenotypes were classified into 10 clusters: intraocular pressure, anterior chamber size, central corneal thickness, cup-to-disc ratio, disc size, cup size, corneal hysteresis, retinal nerve fiber layer thickness, cup shape, and peripapillary atrophy. Random-effects meta-analyses were performed for each cluster. For clusters with n ≥ ۱۰ h2 estimates, we also performed subgroup and meta-regression analyses. The literature search yielded 53 studies. The h2 of primary open-angle glaucoma ranged from 0.17 to 0.81, and was 0.65 for primary angle-closure glaucoma in a single study. The pooled endophenotype h2 estimates were intraocular pressure, 0.43 (0.38–۰٫۴۸); anterior chamber size, 0.67 (0.60–۰٫۷۴); central corneal thickness, 0.81 (0.73–۰٫۸۷); cup-to-disc ratio, 0.56 (0.44–۰٫۶۸); disc size, 0.61 (0.37–۰٫۸۱); cup size, 0.58 (0.35–۰٫۷۸); corneal hysteresis, 0.40 (0.29–۰٫۵۱); retinal nerve fiber layer thickness, 0.73 (0.42–۰٫۹۱); cup shape, 0.62 (0.22–۰٫۹۰); and peripapillary atrophy, 0.73 (0.70–۰٫۷۵). We identified mean age, ethnicity, and study design as major sources of heterogeneity. Our results confirm the strong influence of genetic factors on glaucoma and its endophenotypes. These pooled h2 estimates provide the most accurate assessment to date of the total genetic variation that can ultimately be explained by gene-finding studies.

Background

Glaucoma, the second leading cause of irreversible blindness in the world, is asymptomatic, insidious, and is expected to affect over 100 million people by the year 2040. Glaucoma is a generalized term for a group of progressive neurodegenerative optic nerve disorders characterized by the loss of retinal ganglion cells, thinning of the retinal nerve fiber layer thickness, and visual field loss. Several different types of glaucoma exist, with three major adult-onset variants. The first is primary open-angle glaucoma (POAG), where the anterior chamber angle remains open, but insufficient outflow of aqueous humor through the trabecular meshwork results in increased intraocular pressure (IOP), leading to optic nerve damage and visual field loss.The second variant is normal-tension glaucoma, where optic nerve damage occurs while IOP remains within normal limits. Finally, in primary angle-closure glaucoma (PACG), the increase in IOP is related to a progressive shallowing of the anterior chamber angle.These forms of glaucoma have complex inheritance where multiple genetic variants and environmental factors, in addition to their interactions, contribute to disease risk.