Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank
| dc.contributor.author | Mulugeta, A. | |
| dc.contributor.author | Zhou, A. | |
| dc.contributor.author | King, C. | |
| dc.contributor.author | Hyppönen, E. | |
| dc.date.issued | 2020 | |
| dc.description | Link to a related website: https://www.nature.com/articles/s41380-019-0486-1.pdf, Open Access via Unpaywall | |
| dc.description.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. | |
| dc.identifier.citation | Molecular Psychiatry, 2020; 25(7):1469-1476 | |
| dc.identifier.doi | 10.1038/s41380-019-0486-1 | |
| dc.identifier.issn | 1359-4184 | |
| dc.identifier.issn | 1476-5578 | |
| dc.identifier.uri | https://hdl.handle.net/11541.2/138719 | |
| dc.language.iso | en | |
| dc.publisher | Springer Science and Business Media LLC | |
| dc.rights | Copyright 2019 The Author(s) | |
| dc.source.uri | https://doi.org/10.1038/s41380-019-0486-1 | |
| dc.subject | depression | |
| dc.subject | genetics | |
| dc.title | Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank | |
| dc.type | Journal article | |
| pubs.publication-status | Published | |
| ror.mmsid | 9916307707701831 |