We thank Dr Zhang for their interest in our study [1, 2], and concur that superficial reading of our paper or others on Mendelian Randomization may lead to erroneous interpretation. We are grateful for the opportunity to rectify some of the issues raised.

We would like to point out that genes are conferred at the point of conception. Therefore, it is reasonable to expect that genetic causal associations found in older individuals would be present from birth [2]. Furthermore, myopia onset and progression may continue beyond childhood, into early adulthood [3]. Our findings, which identified a bidirectional genetic causal association between myopia and primary open angle glaucoma (POAG) using multiple Mendelian Randomization models, were based on known genetic variants identified from several genome-wide association studies (GWAS) involving both Asian and European populations [4,5,6,7,8]. Consistent trends were found in the Asian cohorts although these did not reach statistical significance seen in the European cohorts, likely due to the relatively smaller Asian cohort sizes in GWAS literature. Genetic variants that have been consistently identified by GWAS in myopia and POAG indicate a strong genetic basis for both diseases, even in late-onset glaucoma. However, it is clear that both conditions are influenced by multiple factors that genetics may not sufficiently account for.

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