Haibo Liang,1,2,* Qihang Wu,1,2,* Shu Yang,1,2,* Shuhao Zhang,1,2 Jiansen Miao,1,2 Haiming Jin,1,2 Xiangyang Wang1,2 

1Division of Spine Surgery, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2School of The Second Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiangyang Wang, Email xiangyangwang@wmu.edu.cn; Haiming Jin, Email kkjinhaiming@126.com

Purpose: Neck pain (NP) is a multifactorial disorder that leads to severe disability. This study aimed to investigate whether potential risk factors have a causal effect on NP at the genetic level using a two-sample Mendelian randomization (MR) analysis.
Methods: Summary-level data for potential risk factors, including distress, anxiety disorder, depression, mood, sleep disorder, loneliness, education, alcohol consumption, smoking, time spent using the computer, and physical activity, as well as NP, were obtained from multiple large-scale Genome-Wide Association Studies (GWAS). Instrumental variables (IVs) were extracted from these datasets. We employed inverse variance weighting (IVW), weighted median, and MR-Egger regression methods to assess causal effects. Heterogeneity was evaluated using MR-Egger regression and IVW, while horizontal pleiotropy was assessed using MR-PRESSO analysis and MR-Egger regression.
Results: The IVW results showed that major depressive disorder (OR = 1.51, 95% CI: 1.15, 1.98, p = 3.40× 10− 3) and experiencing mood swings (OR = 2.73, 95% CI: 1.57, 4.75, p = 3.86× 10− 4) were positively associated with NP and years of schooling (OR = 0.504, 95% CI: 0.410, 0.619, p = 6.55× 10− 11) was negatively associated with NP. Additionally, loneliness (OR = 16.0, 95% CI: 1.29– 198, p = 0.0307) showed a suggestive association with NP. As for the other factors we did not find a clear causal relationship (All p-values > 0.05).
Conclusion: This two-sample MR study provides genetic evidence supporting a causal relationship between major depressive disorder, mood swings, and years of schooling with NP, while loneliness showed a potential association. These findings highlight the critical role of psychosocial factors, such as depression, mood swings, and education level, in the prevention and management of NP. Our results may offer new insights for clinicians to develop targeted intervention strategies aimed at reducing the incidence of NP.

Keywords: genome-wide association study, Mendelian randomization analysis, neck pain, psychosocial factor