Education is a causal risk factor if an intervention that changes educational exposure changes the distribution of the corresponding potential outcome for myopia. An observed statistical association need not have that interpretation. Shared causes such as socioeconomic circumstances, parental behavior, genetic traits, or preference for indoor near work can confound education and myopia. Reverse causality is also possible: children with impaired distance vision may select more reading and indoor study, which can increase educational attainment without education causing the impairment.
The decisive experiment would be a sufficiently large Randomized controlled trial assigning children to meaningfully different durations or intensities of education, maintaining the assigned contrast, measuring refractive error before treatment and repeatedly afterward, and using blinded outcome assessment with complete follow-up. Randomization makes baseline causes of myopia exchangeable between arms in expectation, while assignment precedes the outcome; under adherence, no interference, and consistent measurement, the difference in outcome distributions estimates the causal effect of the assigned education policy. Such a trial would be ethically unacceptable because it deliberately withholds or imposes education, which explains the appeal of quasi-experimental and genetic approaches.
The core instrumental variable assumptions are:
- Instrument relevance: the genetic variant changes educational attainment.
- Instrumental-variable independence: it is independent of unmeasured common causes of education and myopia, after any justified ancestry adjustment.
- The exclusion restriction: it affects myopia only through education, with no horizontal pleiotropy.
For a local average effect one additionally uses instrumental-variable monotonicity. Because the valid instrument supplies variation in education independent of the confounders and has no direct route to the outcome, the instrument-outcome association can be attributed to the education changed by the instrument without measuring every confounder.
Among the education-associated variants in the left panel, larger genetic effects on time in education are associated with more negative refractive error, hence greater myopia. Under the stated assumptions, the fitted negative slope supports a causal effect of more education on increased myopia. In the reverse direction, the myopia-associated variants in the right panel show a much weaker slope whose confidence band includes zero, so the figure gives little evidence that genetically increased myopia causally increases time in education. The asymmetry supports education-to-myopia causation over reverse causation, subject to the Mendelian-randomization assumptions.
Three useful extensions are:
- Replicate the bidirectional Mendelian randomization in independent, larger cohorts and ancestries, using nonoverlapping discovery and outcome samples to improve precision and reduce winner's-curse and population-specific artifacts.
- Apply pleiotropy-robust analyses such as weighted-median, mode-based, and MR-Egger estimates, inspect heterogeneity and leave-one-variant-out results, and use biologically distinct instrument sets. Agreement despite different sensitivities to invalid instruments strengthens the exclusion restriction.
- Triangulate with a design based on an independent source of causal variation, such as compulsory-schooling-law changes or another natural experiment, and with longitudinal refractive measurements. Agreement across designs with different biases is stronger evidence than enlarging one genetic analysis alone.
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