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

Author:

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

Abstract

BackgroundObservational studies have reported the association between fatigue and coronary artery disease (CAD), but the causal association between fatigue and CAD is unclear.MethodWe 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.ResultSelf-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.ConclusionThe MR analysis reveals a causal relationship between self-reported fatigue and CAD. The results should be interpreted with caution due to horizontal pleiotropy.

Publisher

Frontiers Media SA

Subject

Psychiatry and Mental health

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