Liang Haibo, Wu Qihang, Yang Shu, Zhang Shuhao, Miao Jiansen, Jin Haiming, Wang Xiangyang
Division 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.
School of The Second Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, People's Republic of China.
J Pain Res. 2025 Apr 25;18:2191-2201. doi: 10.2147/JPR.S508287. eCollection 2025.
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.
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.
The IVW results showed that major depressive disorder (OR = 1.51, 95% CI: 1.15, 1.98, p = 3.40×10) and experiencing mood swings (OR = 2.73, 95% CI: 1.57, 4.75, p = 3.86×10) were positively associated with NP and years of schooling (OR = 0.504, 95% CI: 0.410, 0.619, p = 6.55×10) 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).
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.
颈部疼痛（NP）是一种多因素疾病，会导致严重残疾。本研究旨在通过两样本孟德尔随机化（MR）分析，在基因水平上调查潜在风险因素是否对NP具有因果效应。
从多项大规模全基因组关联研究（GWAS）中获取潜在风险因素的汇总数据，包括困扰、焦虑症、抑郁症、情绪、睡眠障碍、孤独感、教育程度、饮酒、吸烟、使用电脑的时间和身体活动，以及NP的数据。从这些数据集中提取工具变量（IV）。我们采用逆方差加权（IVW）、加权中位数和MR-Egger回归方法来评估因果效应。使用MR-Egger回归和IVW评估异质性，同时使用MR-PRESSO分析和MR-Egger回归评估水平多效性。
IVW结果显示，重度抑郁症（比值比[OR]=1.51，95%置信区间[CI]：1.15，1.98，p=3.40×10）和情绪波动（OR=2.73，95%CI：1.57，4.75，p=3.86×10）与NP呈正相关，而受教育年限（OR=0.504，95%CI：0.410，0.619，p=6.55×10）与NP呈负相关。此外，孤独感（OR=16.0，95%CI：1.29-198，p=0.0307）与NP存在提示性关联。至于其他因素，我们未发现明确的因果关系（所有p值>0.05）。
这项两样本MR研究提供了基因证据，支持重度抑郁症、情绪波动和受教育年限与NP之间存在因果关系，而孤独感显示出潜在关联。这些发现突出了心理社会因素，如抑郁症、情绪波动和教育水平，在NP预防和管理中的关键作用。我们的结果可能为临床医生制定旨在降低NP发病率的针对性干预策略提供新的见解。
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