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

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

Vice Chancellor's Office

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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.

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	https://doi.org/10.1111/cea.14010
Publication status	Published - 30 Nov 2021

Data Availability Statement

The UK Biobank dataset used to conduct the research in this paper is available via application directly to the UK Biobank. Applications are assessed for meeting the required criteria for access, including legal and ethics standards. More information regarding data access can be found here: http://www.ukbiobank.ac.uk/scientists-3/. The code and datasets used to carry out the MR analyses are available on GitHub (https://github.com/abudu-aggrey/Allergic_Disease_Mental_Health_MR).

Acknowledgements

This research has been conducted using the UK Biobank Resource under Application Number 10074. Details of patient and public involvement in the UK Biobank are available online (http://www.ukbiobank.ac.uk/about-biobank-uk/ and https://www.ukbiobank.ac.uk/wp-content/uploads/2011/07/Summary-EGF-consultation.pdf). No patients were specifically involved in setting the research question or the outcome measures, nor were they involved in developing plans for recruitment, design or implementation of this study. No patients were asked to advise on interpretation or writing up of results. There are no specific plans to disseminate the results of the research to study participants, but the UK Biobank disseminates key findings from projects on its website.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

allergic disease
association
asthma
atopic dermatitis
causal
hayfever
Mendelian randomization
mental health

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Cite this

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title = "Investigating the causal relationship between allergic disease and mental health",

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.",

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author = "Ashley Budu-Aggrey and Sally Joyce and Davies, \{Neil M.\} and Lavinia Paternoster and Munaf{\`o}, \{Marcus R.\} and Brown, \{Sara J.\} and Jonathan Evans and Sallis, \{Hannah M.\}",

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AU - Joyce, Sally

AU - Davies, Neil M.

AU - Paternoster, Lavinia

AU - Munafò, Marcus R.

AU - Brown, Sara J.

AU - Evans, Jonathan

AU - Sallis, Hannah M.

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N2 - 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.

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KW - causal

KW - hayfever

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ER -

Investigating the causal relationship between allergic disease and mental health

Abstract

Data Availability Statement

Acknowledgements

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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