Abstract
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 × 10−130), anxiety (OR=1.25, 95% CI: 1.18–1.33, p = 6.5 × 10−13), bipolar disorder (ORself-report=1.29, 95% CI: 1.12–1.47, p = 2.8 × 10−4) and neuroticism (β = 0.38, 95% CI: 0.36–0.41, p = 6.8 × 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.
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 × 10−130), anxiety (OR=1.25, 95% CI: 1.18–1.33, p = 6.5 × 10−13), bipolar disorder (ORself-report=1.29, 95% CI: 1.12–1.47, p = 2.8 × 10−4) and neuroticism (β = 0.38, 95% CI: 0.36–0.41, p = 6.8 × 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1449-1458 |
| Number of pages | 10 |
| Journal | Clinical and Experimental Allergy |
| Volume | 51 |
| Issue number | 11 |
| Early online date | 5 Oct 2021 |
| DOIs | |
| Publication status | Published - Nov 2021 |
Bibliographical note
Funding Information:AB‐A, ND, LP, MRM and HMS work in a research unit funded by the UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/7). LP received funding from the British Skin Foundation (8010 Innovative Project) and the Academy of Medical Sciences Springboard Award, which is supported by the Wellcome Trust, The Government Department for Business, Energy and Industrial Strategy, the Global Challenges Research Fund and the British Heart Foundation [SBF003\1094]. HMS is supported by the European Research Council (Grant ref: 758813 MHINT). This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. SJB holds a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z) and a British Skin Foundation large project grant. NMD is supported by a Norwegian Research Council Grant number 295989. The funders had no influence on study design, data collection and analysis, decision to publish or preparation of the manuscript
Publisher Copyright:
© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.
Keywords
- allergic disease
- association
- asthma
- causal
- atopic dermatitis
- hay fever
- Mendelian randomization
- mental health
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