University of South Australia and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia, and Addis Ababa University, Addis Ababa, Ethiopia.
University of Washington, Seattle.
Arthritis Care Res (Hoboken). 2023 Apr;75(4):885-892. doi: 10.1002/acr.24884. Epub 2022 Nov 17.
In this Mendelian randomization (MR) study, the objective was to investigate the causal effect of metabolically different adiposity subtypes on osteoarthritis.
We performed 2-sample MR using summary-level data for osteoarthritis (10,083 cases and 40,425 controls) from a genome-wide association using the UK Biobank, and for site-specific osteoarthritis from the Arthritis Research UK Osteoarthritis Genetics consortium. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral, and favorable). Primary analysis was performed using inverse variance weight (IVW), with additional sensitivity analysis from different MR methods. We further applied a nonlinear MR using UK Biobank data to understand the nature of the adiposity-osteoarthritis relationship.
Greater metabolically unfavorable and metabolically neutral adiposity were associated with higher odds of osteoarthritis (IVW odds ratio [OR] 1.56 [95% confidence interval (95% CI) 1.31, 1.85] and OR 1.60 [95% CI 1.15, 2.23], respectively). The estimate for the association between metabolically favorable adiposity and osteoarthritis was similar, although with notable imprecision (OR 1.55 [95% CI 0.70, 3.41]). Using site-specific osteoarthritis, metabolically unfavorable, neutral, and favorable adiposity were all associated with higher odds of knee osteoarthritis (OR 1.44 [95% CI 1.04, 1.98], OR 2.28 [95% CI 1.04, 4.99], and OR 6.80 [95% CI 2.08, 22.19], respectively). We found generally consistent estimates with a wider confidence interval crossing the null from other MR methods. The nonlinear MR analyses suggested a nonlinear relationship between metabolically unfavorable adiposity and osteoarthritis (P = 0.003).
Metabolic abnormalities did not explain the association between greater adiposity and the risk of osteoarthritis, which might suggest that the association is largely due to a mechanical effect on the joints.
在这项孟德尔随机化（MR）研究中，我们旨在探究代谢不同的肥胖亚型对骨关节炎的因果效应。
我们使用英国生物库的全基因组关联研究中骨关节炎（10083 例病例和 40425 例对照）和关节炎研究英国骨关节炎遗传学联合会的特定部位骨关节炎的汇总水平数据进行了两样本 MR。我们使用了 3 类遗传工具，这些工具均能增加体重指数，但与不同的代谢特征相关（不利、中性和有利）。主要分析采用逆方差加权（IVW），并采用不同的 MR 方法进行额外的敏感性分析。我们进一步使用英国生物库数据进行非线性 MR，以了解肥胖与骨关节炎之间关系的性质。
代谢上不利和中性的肥胖与骨关节炎的发生风险更高相关（IVW 比值比[OR]分别为 1.56[95%置信区间（95%CI）为 1.31，1.85]和 1.60[95%CI 为 1.15，2.23]）。代谢上有利的肥胖与骨关节炎之间的关联估计值相似，但精确度较低（OR 为 1.55[95%CI 为 0.70，3.41]）。使用特定部位骨关节炎，代谢上不利、中性和有利的肥胖均与膝关节骨关节炎的发生风险增加相关（OR 分别为 1.44[95%CI 为 1.04，1.98]、2.28[95%CI 为 1.04，4.99]和 6.80[95%CI 为 2.08，22.19]）。我们从其他 MR 方法中得到了大致一致的估计值，置信区间更宽，跨越了零界值。非线性 MR 分析表明，代谢上不利的肥胖与骨关节炎之间存在非线性关系（P=0.003）。
代谢异常并不能解释肥胖与骨关节炎风险之间的关联，这可能表明这种关联在很大程度上是由于对关节的机械作用所致。
