Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank
Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank
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DOI：
10.1038/s41380-019-0486-1
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发表时间：
2020-07-01
影响因子：
11
通讯作者：
Hypponen, Elina
中科院分区：
文献类型：
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作者：
Mulugeta, Anwar;Zhou, Ang;Hypponen, Elina
抑郁症影响个人生活的各个方面，但与健康因果影响有关的证据有限。我们使用了来自 337,536 名英国生物银行参与者的信息，并对重度抑郁症 (MDD) 遗传风险评分 (GRS) 和 925 种疾病结果之间进行了无假设表型范围关联分析。通过多重测试校正显着性阈值（P < 1.9 x 10(-3)）的GRS-疾病结果关联随后进行孟德尔随机化（MR）分析以测试因果关系。在全表型发现阶段，MDD GRS 与 22 种不同的疾病相关，其中观察到 MDD 诊断和相关并发症（包括焦虑和睡眠障碍）的最强信号。在反方差加权 MR 分析中，MDD 与多种炎症和出血性胃肠道疾病相关，包括食管炎（OR 1.32，95% CI 1.18-1.48）、非感染性胃肠炎（OR 1.25，95% CI 1.06-1.48）、胃肠道出血（OR 1.26，95% CI 1.11-1.43）和肠道大肠杆菌感染（OR 3.24，95% CI 1.74-6.02）。还观察到泌尿系统症状/疾病（OR 1.36，95% CI 1.19-1.56）、哮喘（OR 1.23，95% CI 1.06-1.44）和呼吸痛（OR 1.28，95% CI 1.14-1.44）的信号。 MDD 与脂质代谢紊乱（OR 1.22，95% CI 1.12-1.34）和缺血性心脏病（OR 1.30，95% CI 1.15-1.47）相关。排除多效性变异的敏感性分析提供了一致的关联。我们的研究表明 MDD 与多种疾病之间存在因果关系，表明共病负担显着。 MDD 的早期发现和治疗非常重要，并且应选择治疗策略以尽量减少相关并发症的风险。
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 x 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 intestinalE.coliinfections (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.