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Comment on: ‘Risk of inappropriate causal inference in Mendelian randomization studies on myopia’

Eye volume 39, page 387 (2025)Cite this article

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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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References

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Author information

Authors and Affiliations

  1. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore

    Rachel S. Chong & Cheng Ching-Yu Cheng

  2. Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore

    Rachel S. Chong & Cheng Ching-Yu Cheng

  3. Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Cheng Ching-Yu Cheng

  4. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Cheng Ching-Yu Cheng

Authors
  1. Rachel S. Chong
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  2. Cheng Ching-Yu Cheng
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Contributions

RSC: conceptualization, writing—original draft; CYC: writing—editing & review.

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Correspondence to Rachel S. Chong.

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Chong, R.S., Cheng, C.CY. Comment on: ‘Risk of inappropriate causal inference in Mendelian randomization studies on myopia’. Eye 39, 387 (2025). https://doi.org/10.1038/s41433-024-03398-2

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