Background: Observational studies have reported an association between allergic disease and mental health, but a causal relationship has not been established. Here, we use Mendelian randomization (MR) to investigate a possible causal relationship between atopic disease and mental health phenotypes. Methods:The observational relationship between allergic disease and mental health was investigated in UK Biobank. The direction of causality was investigated with bidirectional two-sample MR using summary-level data from published genome-wide association studies. A genetic instrument was derived from associated variants for a broad allergic disease phenotype to test for causal relationships with various mental health outcomes. We also investigated whether these relationships were specific to atopic dermatitis (AD), asthma or hayfever. Given the multiple testing burden, we applied a Bonferroni correction to use an individual test p-value threshold of .0016 (32 tests). Results:We found strong evidence of an observational association between the broad allergic disease phenotype and depression (OR self-report =1.45,

Background Observational studies have reported an association between allergic disease and mental health, but a causal relationship has not been established. Objective To use Mendelian Randomization (MR) to investigate a possible causal relationship between atopic disease and mental health phenotypes. Methods The observational relationship between allergic disease and mental health was investigated in UK Biobank. The direction of causality was investigated with bidirectional two-sample MR using summary-level data from published genome-wide association studies. A genetic instrument was derived from associated variants for a broad allergic disease phenotype to test for causal relationships with various mental health outcomes. Genetic instruments were also derived for mental health conditions to assess causality in the reverse direction. We also investigated if these relationships were specific to atopic dermatitis (AD), asthma or hay fever. Results The broad allergic disease phenotype was phenotypically associated with most measures of mental health, but we found little evidence of causality in either direction. However, we did find evidence of genetic liability for bipolar disorder causally influencing hay fever risk (OR=0.94 per doubling odds of bipolar disorder risk; 95%CI=0.90-0.99; P-value=0.02), but evidence of a phenotypic association was weak. Conclusions Few of the phenotypic associations between allergic disease and mental health were replicated. Any causal effects we detected were considerably attenuated compared to the phenotypic association. This suggests that most co-morbidity observed clinically is unlikely to be causal.