Investigating the causal relationship between allergic disease and mental health

Ashley Budu-Aggrey; Sally Joyce; Neil M Davies; Lavinia Paternoster; Marcus R Munafò; Sara J Brown; Jonathan Evans; Hannah M Sallis

doi:10.1111/cea.14010

Investigating the causal relationship between allergic disease and mental health

Clin Exp Allergy. 2021 Nov;51(11):1449-1458. doi: 10.1111/cea.14010. Epub 2021 Oct 5.

Authors

Ashley Budu-Aggrey^{1

2}, Sally Joyce², Neil M Davies^{1

2

3}, Lavinia Paternoster^{1

2}, Marcus R Munafò^{1

4}, Sara J Brown⁵, Jonathan Evans^{2

6}, Hannah M Sallis^{1

2

4

6}

Affiliations

¹ Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
² Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.
³ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ School of Psychological Science, University of Bristol, Bristol, UK.
⁵ Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
⁶ Centre for Academic Mental Health, Population Health Sciences, University of Bristol, Bristol, UK.

PMID: 34611950
DOI: 10.1111/cea.14010

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 (OR_self-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 (OR_self-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.

Keywords: Mendelian randomization; allergic disease; association; asthma; atopic dermatitis; causal; hayfever; mental health.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anxiety Disorders
Dermatitis, Atopic*
Genome-Wide Association Study*
Humans
Mendelian Randomization Analysis
Mental Health
Polymorphism, Single Nucleotide

Abstract

Publication types

MeSH terms

Grants and funding