Tang Xijie, Li Qiu, Li Zhang-Hua
Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, 430000, China.
Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430077, China.
Heliyon. 2024 Apr 26;10(9):e30272. doi: 10.1016/j.heliyon.2024.e30272. eCollection 2024 May 15.
The causal association of educational attainment (EA) with intervertebral disc degeneration (IVDD) or low back pain (LBP), and the mediating effect of metabolic syndrome (MetS) in this association, is not studied to date. In this study, using summary statistics of genome-wide association studies primarily conducted in the individuals of European ancestry, Mendelian randomization (MR) analyses were performed to investigate: (1) the total and direct effects of EA on IVDD and LBP, (2) bidirectional associations of EA with MetS or the components of MetS, (3) causal effects of MetS or its components on IVDD and LBP, and (4) mediating effects of MetS or its components on the causal associations of EA with IVDD and LBP. Univariable MR analysis demonstrated that genetically proxied EA was inversely associated with IVDD (ORIVW: 0.90; 95 % CI: 0.87-0.92) and LBP (ORIVW: 0.86; 95 % CI: 0.84-0.89). Consistent results were obtained after adjusting for potential confounders (cognition, economic level, smoking traits, and metabolic factors). Mediation analysis proved that the effect of EA on IVDD mediated by MetS, waist circumference, and high-density lipoprotein cholesterol was 11.38 %, 9.22 %, and 2.17 %, respectively. Besides, MetS mediated 8.42 % and waist circumference mediated 5.81 % of the EA effects on LBP, respectively. Our findings provided support for MetS mediating the causal protective effects of EA on IVDD and LBP, which provided causal evidence to the etiology and intervention targets of IVDD and LBP.
教育程度（EA）与椎间盘退变（IVDD）或腰痛（LBP）之间的因果关联，以及代谢综合征（MetS）在此关联中的中介作用，迄今为止尚未得到研究。在本研究中，利用主要在欧洲血统个体中进行的全基因组关联研究的汇总统计数据，进行了孟德尔随机化（MR）分析，以调查：（1）EA对IVDD和LBP的总体和直接影响；（2）EA与MetS或MetS各组分的双向关联；（3）MetS或其组分对IVDD和LBP的因果影响；（4）MetS或其组分对EA与IVDD和LBP因果关联的中介作用。单变量MR分析表明，遗传代理的EA与IVDD（ORIVW：0.90；95%CI：0.87 - 0.92）和LBP（ORIVW：0.86；95%CI：0.84 - 0.89）呈负相关。在调整潜在混杂因素（认知、经济水平、吸烟特征和代谢因素）后获得了一致的结果。中介分析证明，MetS、腰围和高密度脂蛋白胆固醇介导的EA对IVDD的影响分别为11.38%、9.22%和2.17%。此外，MetS和腰围分别介导了EA对LBP影响的8.42%和5.81%。我们的研究结果支持了MetS介导EA对IVDD和LBP的因果保护作用，这为IVDD和LBP的病因学和干预靶点提供了因果证据。
