Qi Xiaoyi, Wang Shijia, Qiu Liangxian, Chen Xiongbiao, Huang Qianwen, Ouyang Kunfu, Chen Yanjun
Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China.
Medical College, Shantou University, Shantou, China.
Front Psychiatry. 2023 Sep 20;14:1166689. doi: 10.3389/fpsyt.2023.1166689. eCollection 2023.
Observational studies have reported the association between fatigue and coronary artery disease (CAD), but the causal association between fatigue and CAD is unclear.
We conducted a bidirectional Mendelian randomization (MR) study using publicly available genome-wide association studies (GWAS) data. The inverse-variance weighted (IVW) method was used as the primary analysis. We performed three complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) to evaluate the sensitivity and horizontal pleiotropy of the results.
Self-reported fatigue had a causal effect on coronary artery atherosclerosis (CAA) (OR 1.047, 95%CI 1.033-1.062), myocardial infarction (MI) (OR 1.027 95%CI 1.014-1.039) and coronary heart disease (CHD) (OR 1.037, 95%CI 1.021-1.053). We did not find a significant reverse causality between self-reported fatigue and CAD. Given the heterogeneity revealed by MR-Egger regression, we employed the IVW random effect model. For the examination of fatigue on CHD and the reverse analysis of CAA, and MI on fatigue, the MR-PRESSO test found horizontal pleiotropy. No significant outliers were found.
The MR analysis reveals a causal relationship between self-reported fatigue and CAD. The results should be interpreted with caution due to horizontal pleiotropy.
观察性研究报告了疲劳与冠状动脉疾病（CAD）之间的关联，但疲劳与CAD之间的因果关系尚不清楚。
我们使用公开可用的全基因组关联研究（GWAS）数据进行了双向孟德尔随机化（MR）研究。采用逆方差加权（IVW）方法作为主要分析方法。我们还进行了三种补充方法，包括加权中位数、MR-Egger回归和MR多效性残差和异常值（MR-PRESSO），以评估结果的敏感性和水平多效性。
自我报告的疲劳对冠状动脉粥样硬化（CAA）（比值比1.047，95%置信区间1.033-1.062）、心肌梗死（MI）（比值比1.027，95%置信区间1.014-1.039）和冠心病（CHD）（比值比1.037，95%置信区间1.021-1.053）有因果效应。我们未发现自我报告的疲劳与CAD之间存在显著的反向因果关系。鉴于MR-Egger回归显示的异质性，我们采用了IVW随机效应模型。对于疲劳对CHD的检验以及CAA和MI对疲劳的反向分析，MR-PRESSO检验发现了水平多效性。未发现显著的异常值。
MR分析揭示了自我报告的疲劳与CAD之间的因果关系。由于存在水平多效性，对结果的解释应谨慎。
