Causal association between self-reported fatigue and coronary artery disease: a bidirectional two-sample Mendelian randomization analysis

Xiaoyi Qi; Shijia Wang; Liangxian Qiu; Xiongbiao Chen; Qianwen Huang; Kunfu Ouyang; Yanjun Chen

doi:10.3389/fpsyt.2023.1166689

Causal association between self-reported fatigue and coronary artery disease: a bidirectional two-sample Mendelian randomization analysis

Front Psychiatry. 2023 Sep 20:14:1166689. doi: 10.3389/fpsyt.2023.1166689. eCollection 2023.

Authors

Xiaoyi Qi^{1

2}, Shijia Wang¹, Liangxian Qiu¹, Xiongbiao Chen¹, Qianwen Huang¹, Kunfu Ouyang³, Yanjun Chen¹

Affiliations

¹ Departments of Cardiology, Peking University Shenzhen Hospital, Shenzhen, China.
² Medical College, Shantou University, Shantou, China.
³ Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China.

Abstract

Background: Observational studies have reported the association between fatigue and coronary artery disease (CAD), but the causal association between fatigue and CAD is unclear.

Method: 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.

Result: 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.

Conclusion: The MR analysis reveals a causal relationship between self-reported fatigue and CAD. The results should be interpreted with caution due to horizontal pleiotropy.

Keywords: GWAS; Mendelian randomization analysis; coronary artery disease; psychiatry symptom; self-reported fatigue.