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

Xianglong Lv,1 Lin Wang,2 Jing Yao,2 Yuanxin Huang2 1Guizhou Medical University, Guiyang, People’s Republic of China; 2The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of ChinaCorrespondence: Yuanxin Huang, Email [email protected]: 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: depression, bidirectional Mendelian randomization, cervical spondylosis, mental health, genetic correlation analysis, quality of life