Circulating metabolites and depression: a bidirectional Mendelian randomization

Yankai Dong; Zengxiao Zou; Pin Deng; Xiaoping Fan; Chunlin Li

doi:10.3389/fnins.2023.1146613

Circulating metabolites and depression: a bidirectional Mendelian randomization

Front Neurosci. 2023 Apr 21:17:1146613. doi: 10.3389/fnins.2023.1146613. eCollection 2023.

Authors

Yankai Dong^#^{1

2}, Zengxiao Zou^#^{1

2}, Pin Deng^#³, Xiaoping Fan^{1

2}, Chunlin Li⁴

Affiliations

¹ Department of Cardiovascular Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
² The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
³ Department of Hand and Foot Surgery, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China.
⁴ Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

^# Contributed equally.

Abstract

Background: Studies have shown an association between depression and circulating metabolites, but the causal relationship between them has not been elucidated. The purpose of this study was to elucidate the causal relationship between circulating metabolites and depression and to explore the role of circulating metabolites in depression.

Methods: In this study, the top single-nucleotide polymorphisms (SNPs) associated with circulating metabolites (n = 24,925) and depression (n = 322,580) were obtained based on the publicly available genome-wide association study using two-sample Mendelian randomization (MR). SNP estimates were summarized through inverse variance weighted, MR Egger, weighted median, MR pleiotropy residual sum and outlier, and "leave-one-out" methods.

Results: Apolipoprotein A-I (OR 0.990, 95% CI 981-0.999) and glutamine (OR 0.985, 95% CI 0.972-0.997) had protective causal effects on depression, whereas acetoacetate (OR 1.021, 95% CI 1.009-1.034), glycoproteins (OR 1.005, 95% CI 1.000-1.009), isoleucine (OR 1.013, 95% CI 1.002-1.024), and urea (OR 1.020, 95% CI 1.000-1.039) had an anti-protective effect on depression. Reversed MR showed no effect of depression on the seven circulating metabolites.

Conclusion: In this study, MR analysis showed that apolipoprotein A-I and glutamine had a protective effect on depression, and acetoacetate, glycoprotein, isoleucine, glucose, and urea may be risk factors for depression. Therefore, further research must be conducted to translate the findings into practice.

Keywords: Mendelian randomization; bidirectional; circulating metabolites; depression; instrumental variable.

Grants and funding

CL received grants from the Science and Technology Plan Project of Jinan (202019152), XF received grants from the Project of the State Key Laboratory of Dampness Syndrome of Traditional Chinese Medicine jointly established by the province and the ministry (No. SZ2022KF10), Scientific Research Initiation Project of Guangdong Provincial Hospital of Traditional Chinese Medicine (No. 2021KT1709), and Guangdong Provincial Key Laboratory of Research on Emergency in TCM (No. 2017B030314176).