A Hypothesis-Free Approach to Identifying Potential Effects of Relative Age in School Year: an Instrumental Variable Phenome-Wide Association Study in the UK Biobank.

A child's relative age within their school year ('relative age') is associated with educational attainment and mental health. However, hypothesis driven studies often re-examine the same outcomes and exposure, potentially leading to confirmation and reporting biases, and missing unknown effects. Hypothesis-free outcome-wide analyses can potentially overcome these limitations. We conducted a hypothesis-free investigation of the effects of relative age within school year. We used an instrumental variable (IV)-pheWAS in the UK Biobank (participants aged 40-69 years at baseline), using the PHESANT software package. We created two IVs for relative age: being born in September vs. August (n=64 075) and week of birth (n=383 309). Outcomes passing the Bonferroni-corrected P value threshold for either instrument were plotted to identify a discontinuity at the school year transition. 13 traits associated with at least one of the instruments showed a discontinuity. Previously identified effects included those with a younger relative age being less likely to have educational qualifications and more likely to have started smoking at a younger age. We detected a few associations not explored by previous studies. For example, those with younger relative age had better lung function as adults. Hypothesis-free approaches could help address confirmation and reporting biases in epidemiology.