Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (1): 28-36.doi: 10.6040/j.issn.1671-7554.0.2024.1213

• Special Issue—Mechanistic Evidence and Clinical Translation in Mental and Sleep Disorders • Previous Articles     Next Articles

Association of depression and antidepressant drug target genes with sleep apnea based on two-sample Mendelian randomization

CHEN Chan, LI Juzhang, HE Wen, WU Qiaozhen   

  1. Department of Respiratory and Critical Care Medicine, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou 215000, Jiangsu, China
  • Published:2026-01-27

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Abstract: Objective To explore the causal relationship between obstructive sleep apnea(OSA)and depression and to find potential targets for the treatment of OSA with depression from the targets of antidepressant drugs. Methods Data on genetic variants associated with depression and OSA were obtained from genome-wide association studies(GWAS). The coding gene data of antidepressant drug targets were obtained from eQTLGen Consortium website. TSMR analysis was performed with depression and antidepressant drug targets as exposure and OSA as outcome. Single nucleotide polymorphisms(SNPS)strongly associated with exposure variables were used as instrumental variables, and inverse-variance weighted(IVW)was used as the main analysis method while MR-Egger, weighted median(WME), simple mode(SM)and weighted mode(WM)were used as supplementary evidence for TSMR analysis. Sensitivity analysis was performed with MR-PRESSO and leave-one-out method, excluding each instrumental variable to observe its influence on the overall estimation. Cochrans Q test and MR-Egger intercept test were used to determine heterogeneity and horizontal pleiotropy. Funnel plot was used to assess potential bias. Results IVW analysis showed that there was a causal relationship between genetic prediction of depression and increased risk of OSA(OR=1.180, 95%CI=1.065-1.306, P=0.001). Cochrans Q test and MR-Egger intercept test showed no heterogeneity and horizontal pleiotropy. MR-PRESSO test and leave-one-out test indicated that the effect of excluding any SNP on causality was not significant, and the funnel plot showed that the left and right distribution was roughly uniform. The expression of antidepressant drug targets HTR3A(OR=1.174,95%CI= 1.022-1.350,P=0.024)and GRIN3A(OR=1.227,95%CI= 1.126-1.338,P<0.001)had a causal relationship with increased risk of OSA. Conclusion Depression can increase the risk of OSA, and the antidepressant drug targets HTR3A and GRIN3A may be candidate drug targets for the treatment of depression with OSA.

Key words: Mendelian randomization, Depression, Obstructive sleep apnea, Antidepressant drug targets

CLC Number: 

  • R749
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