Investigating the causal relationship between allergic disease and mental health
10 May 2021
New preprint by Ashley Budu-Aggrey, Sally Joyce, Neil Davies, Lavinia Paternoster, Marcus Munafò, Sara Brown, Jonathan Evans and Hannah Sallis.
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.
Clinical Implication We found little evidence that genetic predisposition to allergic disease causes mental ill-health, and vice versa, which suggests that intervening to prevent onset of allergic disease is unlikely to directly prevent the onset of mental ill-health.
Mendelian randomization effect estimates suggest that the phenotypic association between allergic disease and mental health is likely to be inflated
Causal analysis was unable to corroborate the phenotypic associations observed between allergic disease and mental health phenotypes
Intervening on an individual’s allergic disease is not likely to directly improve their mental health
Capsule Summary Mendelian Randomization suggests that evidence of a causal relationship between allergic disease and mental health phenotypes is weak. It is unlikely that intervening to prevent onset of allergic disease will prevent poor mental health.