MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom; Musculoskeletal Research Unit, University of Bristol, Bristol, UK.
Osteoarthritis Cartilage. 2024 Jun;32(6):719-729. doi: 10.1016/j.joca.2023.12.003. Epub 2023 Dec 30.
Spinal stenosis is a common condition among older individuals, with significant morbidity attached. Little is known about its risk factors but degenerative conditions, such as osteoarthritis (OA) have been identified for their mechanistic role. This study aims to explore causal relationships between anthropometric risk factors, OA, and spinal stenosis using Mendelian randomisation (MR) techniques.
We applied two-sample MR to investigate the causal relationships between genetic liability for select risk factors and spinal stenosis. Next, we examined the genetic relationship between OA and spinal stenosis with linkage disequilibrium score regression and Causal Analysis Using Summary Effect estimates MR method. Finally, we used multivariable MR (MVMR) to explore whether OA and body mass index (BMI) mediate the causal pathways identified.
Our analysis revealed strong evidence for the effect of higher BMI (odds ratio [OR] = 1.54, 95%CI: 1.41-1.69, p-value = 2.7 × 10), waist (OR = 1.43, 95%CI: 1.15-1.79, p-value = 1.5 × 10) and hip (OR = 1.50, 95%CI: 1.27-1.78, p-value = 3.3 × 10) circumference on spinal stenosis. Strong evidence of causality was also observed for higher bone mineral density (BMD): total body (OR = 1.21, 95%CI: 1.12-1.29, p-value = 1.6 × 10), femoral neck (OR = 1.35, 95%CI: 1.09-1.37, p-value = 7.5×10), and lumbar spine (OR = 1.38, 95%CI: 1.25-1.52, p-value = 4.4 × 10). We detected high genetic correlations between spinal stenosis and OA (rg range: 0.47-0.66), with Causal Analysis Using Summary Effect estimates results supporting a causal effect of OA on spinal stenosis (OR = 1.6, 95%CI: 1.41-1.79). Direct effects of BMI, BMD on spinal stenosis remained after adjusting for OA in the MVMR.
Genetic susceptibility to anthropometric risk factors, particularly higher BMI and BMD can increase the risk of spinal stenosis, independent of OA status. These results may inform preventative strategies and treatments.
脊柱狭窄症是老年人常见的疾病，发病率较高。其危险因素知之甚少，但已确定退行性疾病，如骨关节炎（OA）与发病机制有关。本研究旨在应用孟德尔随机化（MR）技术探讨人体测量危险因素、OA 和脊柱狭窄之间的因果关系。
我们应用两样本 MR 分析选择的危险因素遗传易感性与脊柱狭窄之间的因果关系。接下来，我们使用连锁不平衡评分回归和因果分析综合效应估计 MR 方法检验 OA 和脊柱狭窄之间的遗传关系。最后，我们使用多变量 MR（MVMR）探讨 OA 和体重指数（BMI）是否调节了所识别的因果途径。
我们的分析表明，BMI（比值比[OR] = 1.54，95%CI：1.41-1.69，p 值 = 2.7×10）、腰围（OR = 1.43，95%CI：1.15-1.79，p 值 = 1.5×10）和臀围（OR = 1.50，95%CI：1.27-1.78，p 值 = 3.3×10）较高与脊柱狭窄有很强的因果关系。骨密度（BMD）较高也有很强的因果关系：全身（OR = 1.21，95%CI：1.12-1.29，p 值 = 1.6×10）、股骨颈（OR = 1.35，95%CI：1.09-1.37，p 值 = 7.5×10）和腰椎（OR = 1.38，95%CI：1.25-1.52，p 值 = 4.4×10）。我们检测到脊柱狭窄症和 OA 之间的遗传相关性很高（rg 范围：0.47-0.66），因果分析综合效应估计结果支持 OA 对脊柱狭窄症的因果效应（OR = 1.6，95%CI：1.41-1.79）。MVMR 中调整 OA 后，BMI、BMD 对脊柱狭窄症的直接影响仍然存在。
人体测量危险因素的遗传易感性，特别是 BMI 和 BMD 较高，可能会增加脊柱狭窄症的风险，而与 OA 状态无关。这些结果可能为预防策略和治疗提供信息。
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