Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis: A Systematic Review.

Han Lin Wang; Yan Feng Xue; Bao Qiu Cui; Hong Liu; Xin Xin Shen

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Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis: A Systematic Review.

Author: Han Lin WANG ¹ ; Yan Feng XUE ² ; Bao Qiu CUI ¹ ; Hong LIU ¹ ; Xin Xin SHEN ³
Author Information

1. Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong, China.
2. Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030013, Shanxi, China.
3. State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Publication Type:Journal Article
Keywords: Depression; Drug targets; Major depressive disorder; Risk factors; Two-sample Mendelian randomization
MeSH: Humans; Depressive Disorder, Major/genetics*; Depression; Genome-Wide Association Study; Mendelian Randomization Analysis; Risk Factors; Serotonin Plasma Membrane Transport Proteins
From: Biomedical and Environmental Sciences 2024;37(1):85-95
CountryChina
Language:English
Abstract: OBJECTIVE:This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.
METHODS:We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( n = 113,154) and MDD ( n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.
RESULTS:The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.
CONCLUSION:This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.