Abstract
PURPOSE: Lifestyle risk factors are implicated in driving the current surge in myopia prevalence yet, paradoxically, known risk factors explain little of the variation in refractive error in the population. Here, we applied "instrumental variable" (IV) methods designed to avoid reverse causation and decrease confounding bias, to gauge lifestyle risk factor effect sizes. METHODS: Three myopia risk factors (time outdoors, time reading, and sleep duration) were assessed in participants of the Avon Longitudinal Study of Parents and Children: a cross-sectional sample of 2302 children aged 15 years old and a longitudinal sample of 3086 children followed from age 7 to 15 years. Seven IVs were considered jointly: dog ownership, cat ownership, bedtime variability, birth order, and polygenic scores quantifying genetic predisposition to spend additional time outdoors, years in fulltime education, and time asleep overnight. RESULTS: Risk factor effect sizes were 4-fold to 9-fold higher in the IV analyses compared with conventional regression analyses. In IV analyses, one extra hour spent outdoors every day during childhood was associated with a shift toward hyperopia of +0.53 to +0.94 diopters (D), whereas 1 extra hour spent reading every day was associated with a shift toward myopia of -0.44 to -0.88 D. There was inconsistent evidence that sleep duration influenced refractive error. CONCLUSIONS: Myopia risk factor effects were underestimated up to 9-fold in conventional analyses in this sample, compared with IV analyses. TRANSLATIONAL RELEVANCE: We speculate that the effects of lifestyle risk factors for myopia have been underestimated in past studies.