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Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank

Molecular Psychiatry volume 25, pages 1469–1476 (2020)Cite this article

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Abstract

Depression affects all aspects of an individual’s life but evidence relating to the causal effects on health is limited. We used information from 337,536 UK Biobank participants and performed hypothesis-free phenome-wide association analyses between major depressive disorder (MDD) genetic risk score (GRS) and 925 disease outcomes. GRS–disease outcome associations passing the multiple-testing corrected significance threshold (P < 1.9 × 10−3) were followed by Mendelian randomisation (MR) analyses to test for causality. MDD GRS was associated with 22 distinct diseases in the phenome-wide discovery stage, with the strongest signal observed for MDD diagnosis and related co-morbidities including anxiety and sleep disorders. In inverse-variance weighted MR analyses, MDD was associated with several inflammatory and haemorrhagic gastrointestinal diseases, including oesophagitis (OR 1.32, 95% CI 1.18–1.48), non-infectious gastroenteritis (OR 1.25, 95% CI 1.06–1.48), gastrointestinal haemorrhage (OR 1.26, 95% CI 1.11–1.43) and intestinal E.coli infections (OR 3.24, 95% CI 1.74–6.02). Signals were also observed for symptoms/disorders of the urinary system (OR 1.36, 95% CI 1.19–1.56), asthma (OR 1.23, 95% CI 1.06–1.44), and painful respiration (OR 1.28, 95% CI 1.14–1.44). MDD was associated with disorders of lipid metabolism (OR 1.22, 95% CI 1.12–1.34) and ischaemic heart disease (OR 1.30, 95% CI 1.15–1.47). Sensitivity analyses excluding pleiotropic variants provided consistent associations. Our study indicates a causal link between MDD and a broad range of diseases, suggesting a notable burden of co-morbidity. Early detection and management of MDD is important, and treatment strategies should be selected to also minimise the risk of related co-morbidities.

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Acknowledgements

The authors are very grateful to the UK Biobank and UK Biobank Participants. We conducted this research using the UK Biobank Resource under application number 10171. The authors are also thankful to the Australian Research Training Program Scholarship for AM’s studentship fund/support.

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Authors and Affiliations

  1. Australian Centre for Precision Health, University of South Australia Cancer Research Institute, Adelaide, Australia

    Anwar Mulugeta, Ang Zhou, Catherine King & Elina Hyppönen

  2. Department of Pharmacology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia

    Anwar Mulugeta

  3. School of Pharmacy and Medical Sciences, University of South Australia, North Terrace, Adelaide, SA, Australia

    Catherine King

  4. Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, UK

    Elina Hyppönen

  5. South Australian Health and Medical Research Institute, Adelaide, Australia

    Elina Hyppönen

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  1. Anwar Mulugeta
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Contributions

EH and AM conceptualised the study. AM and AZ undertook data management and analyses. AM and EH drafted the paper. All authors interpreted the results, critically revised the paper for intellectual content and approved the final paper.

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Correspondence to Elina Hyppönen.

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Mulugeta, A., Zhou, A., King, C. et al. Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank. Mol Psychiatry 25, 1469–1476 (2020). https://doi.org/10.1038/s41380-019-0486-1

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