Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Diabetologia. 2020 Jul;63(7):1305-1311. doi: 10.1007/s00125-020-05131-6. Epub 2020 Apr 8.
AIMS/HYPOTHESIS: Observational studies have shown a bidirectional association between major depressive disorder (MDD) and cardiometabolic diseases. We conducted a two-sample bidirectional Mendelian randomisation (MR) study to assess the causal associations of MDD with type 2 diabetes, coronary artery disease (CAD) and heart failure and vice versa.
We extracted summary-level data for MDD, type 2 diabetes, CAD and heart failure from corresponding published large genome-wide association studies of individuals mainly of European-descent. In total, 96 SNPs for MDD, 202 SNPs for type 2 diabetes, 44 SNPs for CAD and 12 SNPs for heart failure were proposed as instrumental variables at the genome-wide significance level (p < 5 × 10). The random-effects inverse-variance weighted method was used for the main analyses.
Genetic liability to MDD was significantly associated with type 2 diabetes and CAD at the Bonferroni-corrected significance level. The ORs of type 2 diabetes and CAD were respectively 1.26 (95% CI 1.10, 1.43; p = 6 × 10) and 1.16 (95% CI 1.05, 1.29; p = 0.0047) per one-unit increase in log odds of MDD. There was a suggestive association between MDD and heart failure (OR 1.11 [95% CI 1.01, 1.21]; p = 0.033). We found limited evidence supporting causal effects of cardiometabolic diseases on MDD risk in the reverse MR analyses.
CONCLUSIONS/INTERPRETATION: The present study strengthened the evidence that MDD is a potential risk factor for type 2 diabetes and CAD. Whether MDD is causally related to heart failure needs further study.
All data included in this study were uploaded as supplements and are also publicly available through published GWASs and open GWAS datasets (UK Biobank, 23andMe and Psychiatric Genomics: https://datashare.is.ed.ac.uk/handle/10283/3203; DIAGRAM: http://diagram-consortium.org/downloads.html; CARDIoGRAMplusCD4: www.cardiogramplusc4d.org/; HERMES: http://www.kp4cd.org/datasets/mi). Graphical abstract.
目的/假设：观察性研究表明，重度抑郁症（MDD）和心脏代谢疾病之间存在双向关联。我们进行了两样本双向孟德尔随机化（MR）研究，以评估 MDD 与 2 型糖尿病、冠心病（CAD）和心力衰竭之间以及反之亦然的因果关系。
我们从主要为欧洲血统个体的相应已发表的大型全基因组关联研究中提取了 MDD、2 型糖尿病、CAD 和心力衰竭的汇总水平数据。总共提出了 96 个用于 MDD、202 个用于 2 型糖尿病、44 个用于 CAD 和 12 个用于心力衰竭的全基因组显著水平（p < 5 × 10）的 SNP 作为工具变量。主要分析采用随机效应逆方差加权法。
MDD 的遗传易感性与 2 型糖尿病和 CAD 在 Bonferroni 校正的显著性水平上显著相关。2 型糖尿病和 CAD 的 OR 分别为 1.26（95% CI 1.10, 1.43;p = 6 × 10）和 1.16（95% CI 1.05, 1.29;p = 0.0047），MDD 对数几率每增加一个单位。MDD 与心力衰竭之间存在提示性关联（OR 1.11[95% CI 1.01, 1.21];p = 0.033）。在反向 MR 分析中，我们发现心血管疾病对 MDD 风险的因果影响的证据有限。
结论/解释：本研究加强了 MDD 是 2 型糖尿病和 CAD 潜在危险因素的证据。MDD 是否与心力衰竭有因果关系需要进一步研究。
本研究中包含的所有数据均作为补充上传，也可通过已发表的 GWAS 和开放的 GWAS 数据集（英国生物银行、23andMe 和精神基因组学：https://datashare.is.ed.ac.uk/handle/10283/3203；DIAGRAM：http://diagram-consortium.org/downloads.html；CARDIOGRAMplusCD4：www.cardiogramplusc4d.org/；HERMES：http://www.kp4cd.org/datasets/mi）公开获取。图表摘要。
