Investigating the causal relationship between allergic disease and mental health

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 (ORself-report=1.45, 95% CI: 1.41-1.50, p = 3.6 x 10(-130)), anxiety (OR=1.25, 95% CI: 1.18-1.33, p = 6.5 x 10(-13)), bipolar disorder (ORself-report=1.29, 95% CI: 1.12-1.47, p = 2.8 x 10(-4)) and neuroticism (beta = 0.38, 95% CI: 0.36-0.41, p = 6.8 x 10(-166)). Similar associations were found between asthma, AD, hayfever individually with the mental health phenotypes, although the associations between AD and hayfever with bipolar disorder were weaker. There was little evidence of causality in either direction (all p-values>.02). Conclusion Using MR, we were unable to replicate most of the phenotypic associations between allergic disease and mental health. Any causal effects we detected were considerably attenuated compared with the phenotypic association. This suggests that most comorbidity observed clinically is unlikely to be causal.