P32 Investigating causal associations between eczema and mental health and neurodevelopmental conditions

Abstract Introduction and aims Eczema is a common skin condition with a high global burden, particularly during childhood and adolescence. These periods align with the average age of onset for most mental health and neurodevelopmental conditions. Clinical and population-based observational studies consistently report associations between eczema and adverse mental health, neurodevelopmental and related conditions. However, it is unknown whether these associations reflect causal relationships. Therefore, we aim to examine whether eczema causally contributes to the development of mental health, neurodevelopmental and related conditions. Methods We conducted two-sample Mendelian randomization (MR) analyses to investigate causality between eczema and 30 mental health, neurodevelopmental, and related outcomes. The largest available genome-wide association summary statistics were used in the MR analyses for eczema and each outcome. Results The majority of preliminary MR estimates were lower than the reported observational estimates. Evidence for a causal effect varied, with suggestive evidence for a causal effect observed for some outcomes, while little evidence of causality was observed for others. For example, there is some evidence for a causal effect between eczema and major depression. MR estimates indicate an increased risk of depression associated with genetic liability to eczema odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01–1.04, and an increased risk of eczema associated with genetic liability to depression (OR 1.08, 95% CI 1.02–1.15). These estimates are consistent with observational evidence in adolescence hazard ratio (HR) 1.07, 95% CI 1.06–1.08. Meanwhile, null MR estimates were observed for migraine (HR 0.99, 95% CI 0.98–1.00) compared with observational evidence (HR 1.15, 95% CI 1.13–1.17). Conclusions Our results indicate a potential causal relationship between eczema and major depression. Further work will be conducted to expand these findings to include estimates for additional genetic ancestries, investigate whether the bidirectional relationship is attributable to shared genetic loci, and identify potential underlying mechanisms, including mediating factors. These results could inform clinical management of eczema.