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. 2024 Dec 17:17:4343-4355.
doi: 10.2147/JPR.S488082. eCollection 2024.

Investigating the Gene Relation Between Cervical Spondylosis and Depression: Bidirectional Mendelian Randomization Study

Xianglong Lv  1 , Lin Wang  2 , Jing Yao  2 , Yuanxin Huang  2
Affiliations

Investigating the Gene Relation Between Cervical Spondylosis and Depression: Bidirectional Mendelian Randomization Study

Xianglong Lv et al. J Pain Res. .

Abstract

Background: Previous observational studies have suggested a potential link between depression and cervical spondylosis (CS). While it is known that depression and CS can coexist, the specific relationship between them is not fully understood. We hypothesize that there may be connections between the two conditions, but the independent causal relationship of depression as a risk factor for CS, remains uncertain. This particular study has important implications for the future clinical treatment of depression and cervical spondylosis because Mendelian randomization has not been widely used in this field. We obtained valuable results through big data analysis and have guiding significance for future research.

Methods: We conducted a two-sample Mendelian randomization (MR) study using data from genome-wide association studies to investigate the causal relationship between depression and CS in individuals of European ancestry. Additionally, we examined the impact of CS on susceptibility to depression using large population-level genetic data (number of depression SNPs: 9,761,853; number of CS SNPs: 9,851,867). The primary approach for data analysis was the inverse-variance weighted (IVW) method to estimate potential causal effects. Furthermore, we performed sensitivity analyses utilizing methods such as Manhattan plot (CMplot), linkage disequilibrium (LD), F-filtering, removal of phenoscanner, MR-Egger, weighted median, MR-PRESSO simple mode weighted mode MR pleiotropy test MR heterogeneity assessment leave-one-out analysis to ensure result robustness.

Results: Our findings indicated that an elevated likelihood of CS was linked to depression [IVW odds ratio (OR): 1.322, 95% confidence interval (CI): 1.205-1.441, P=0.01243]. There was reciprocal evidence of causation, with the genetic predisposition to depression significantly heightening susceptibility to CS [IVW odds ratio (OR): 1.426, 95% confidence interval (CI): 1.236-1.651, P=0.01775].

Conclusion: This investigation provides genetic support for a bidirectional causal association between depression and CS. Specifically, individuals with depression are at greater risk of developing CS. Addressing depression may serve as an effective approach in mitigating or preventing the burden of CS and vice versa.

Keywords: bidirectional Mendelian randomization; cervical spondylosis; depression; genetic correlation analysis; mental health; quality of life.

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Conflict of interest statement

The entire group of individuals mentioned in the article have reached a consensus to make revisions and release the content in the journal for public access. Each and every author affirms that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Selected SNPs strongly related to exposure factors, and plotted linear Manhattans and circular Manhattans (A–D).
Figure 2
Figure 2
Depression on CS (A) Mendelian analysis results, (B) heterogeneity analysis, (C) pleiotropy analysis, (D) MR-PRESSO results.
Figure 3
Figure 3
(A) Forest plot of the casual effect of depression on CS; (B) funnel plot of the casual effect of depression on CS.
Figure 4
Figure 4
(A) Leave-one-out plot of the casual effect of depression on CS; (B) scatter plot of the casual effect of depression on CS.
Figure 5
Figure 5
CS on Depression (A) Mendelian analysis results, (B) heterogeneity analysis, (C) pleiotropy analysis, (D) MR-PRESSO results.
Figure 6
Figure 6
(A) Forest plot of the casual effect of CS on depression; (B) funnel plot of the casual effect of CS on depression.
Figure 7
Figure 7
(A) Leave-one-out plot of the casual effect of CS on depression; (B) scatter plot of the casual effect of CS on depression.
Figure 8
Figure 8
The two figures are visual forest plots of the Mendelian randomization analysis of CS and depression (A and B); (A) the casual effect of depression on CS (forest); (B) the casual effect of CS on depression (forest).
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