Lee Young Ho
Department of Rheumatology, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of).
Z Rheumatol. 2019 Jun;78(5):461-466. doi: 10.1007/s00393-018-0505-7.
This study aimed to examine whether smoking behavior is causally associated with osteoarthritis.
A two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods was performed. We used the publicly available summary statistics datasets of smoking behavior genome-wide association studies (GWASs; n = 85,997) as an exposure, and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study and 11,009 controls of European ancestry as an outcome.
We selected four single nucleotide polymorphisms (SNPs) from GWASs of smoking behavior as instrumental variables (IVs) to improve inference. These SNPs were located at CHRNA3 (rs1051730), SLC25A5P5A9 (rs215614), CHRNB3 (rs6474412), and CYP2B6 (rs7260329). The IVW method showed evidence to support an inverse causal association between smoking behavior and osteoarthritis in the knee and hip (beta = -0.056, standard error [SE] = 0.027, p = 0.035). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = -0.005; p = 0.848), but showed no causal association between smoking behavior and osteoarthritis (beta = -0.048, SE = 0.048, p = 0.427). However, the weighted median approach yielded evidence of a negative causal association between smoking behavior and osteoarthritis (beta = -0.056, SE = 0.028, p = 0.046). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity between IV estimates based on the individual variants.
The results of MR analysis support that smoking behavior was causally associated with a reduced risk of osteoarthritis.
本研究旨在探讨吸烟行为与骨关节炎之间是否存在因果关系。
采用逆方差加权法（IVW）、加权中位数法和MR-Egger回归法进行两样本孟德尔随机化（MR）分析。我们将公开可用的吸烟行为全基因组关联研究（GWASs；n = 85,997）的汇总统计数据集作为暴露因素，将arcOGEN研究中7410例骨关节炎患者和11,009例欧洲血统对照的GWAS作为结果。
我们从吸烟行为的GWAS中选择了四个单核苷酸多态性（SNP）作为工具变量（IVs），以改善推断。这些SNP位于CHRNA3（rs1051730）、SLC25A5P5A9（rs215614）、CHRNB3（rs6474412）和CYP2B6（rs7260329）。IVW方法显示有证据支持吸烟行为与膝关节和髋关节骨关节炎之间存在反向因果关系（β = -0.056，标准误[SE] = 0.027，p = 0.035）。MR-Egger回归显示，定向多效性不太可能使结果产生偏差（截距 = -0.005；p = 0.848），但未显示吸烟行为与骨关节炎之间存在因果关系（β = -0.048，SE = 0.048，p = 0.427）。然而，加权中位数法得出了吸烟行为与骨关节炎之间存在负向因果关系的证据（β = -0.056，SE = 0.028，p = 0.046）。Cochran's Q检验和漏斗图表明，基于各个变异体的IV估计之间没有异质性证据。
MR分析结果支持吸烟行为与骨关节炎风险降低之间存在因果关系。
