期刊
CLINICAL AND EXPERIMENTAL ALLERGY
卷 51, 期 11, 页码 1449-1458出版社
WILEY
DOI: 10.1111/cea.14010
关键词
allergic disease; association; asthma; atopic dermatitis; causal; hayfever; Mendelian randomization; mental health
资金
- UK Medical Research Council [MC_UU_00011/1, MC_UU_00011/7]
- British Skin Foundation [8010]
- Academy of Medical Sciences Springboard Award - Wellcome Trust
- Government Department for Business, Energy and Industrial Strategy
- Global Challenges Research Fund
- British Heart Foundation [SBF003\1094]
- European Research Council [758813 MHINT]
- National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust
- Wellcome Trust Senior Research Fellowship in Clinical Science [106865/Z/15/Z]
- British Skin Foundation large project
- Norwegian Research Council [295989]
Observational studies have shown an association between allergic disease and mental health, but using Mendelian randomization, researchers were not able to replicate most of the phenotypic associations between allergic disease and mental health. Any causal effects detected were considerably weaker than the phenotypic association, indicating that most comorbidity observed clinically is unlikely to be causal.
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.
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