Department of Rheumatology, Korea University College of Medicine, Korea University Anam Hospital, 73, Inchon-ro, Seongbuk-gu, Seoul, 02841, South Korea.
Clin Rheumatol. 2018 Nov;37(11):3133-3139. doi: 10.1007/s10067-018-4252-6. Epub 2018 Aug 3.
This study examined whether coffee consumption is causally associated with osteoarthritis. A two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) and weighted median estimates, and the MR-Egger regression method were performed. The publicly available summary statistical datasets of coffee consumption genome-wide association studies (GWASs) meta-analyses on coffee intake from eight Caucasian cohorts (n = 18,176), GWAS meta-analyses of predominately regular-type coffee consumers of European ancestry (n = up to 91,462), and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study with 11,009 controls of European ancestry were evaluated. Four single-nucleotide polymorphisms (SNPs) from GWASs of coffee consumption as instrumental variables (IVs) to improve inference were selected. These SNPs were located at neurocalcin delta (NCALD) (rs16868941), cytochrome p450 oxidoreductase (POR) (rs17685), cytochrome p450 family 1 subfamily A member 1 (CYP1A1) (rs2470893), and neuronal cell adhesion molecule (NRCAM) (rs382140). The IVW method (beta = 0.381, SE = 0.170, p = 0.025) and the weighted median approach (beta = 0.419, SE = 0.206, p = 0.047) showed evidence to support a causal association between coffee consumption and osteoarthritis. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = 0.064; p = 0.549), but showed no causal association between coffee consumption and osteoarthritis (beta = - 0.518, SE = 1.270, p = 0.723). 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 the observation that coffee consumption is causally associated with an increased risk of osteoarthritis.
这项研究旨在探究咖啡摄入是否与骨关节炎存在因果关系。研究采用双样本孟德尔随机化（MR）分析方法，包括逆方差加权（IVW）和加权中位数估计，以及 MR-Egger 回归方法。本研究使用了来自八个白种人队列的咖啡摄入量全基因组关联研究（GWASs）荟萃分析的公开可用汇总统计数据集（n=18176）、欧洲裔主要饮用常规型咖啡的 GWASs 荟萃分析（n=最多 91462），以及在 arcOGEN 研究中对 7410 名骨关节炎患者和 11009 名欧洲裔对照进行的 GWAS。选择了四个来自咖啡消费 GWAS 的单核苷酸多态性（SNP）作为工具变量（IVs）来改善推断，这些 SNP 位于神经钙调蛋白 delta（NCALD）（rs16868941）、细胞色素 P450 氧化还原酶（POR）（rs17685）、细胞色素 P450 家族 1 亚家族 A 成员 1（CYP1A1）（rs2470893）和神经元细胞黏附分子（NRCAM）（rs382140）。IVW 方法（beta=0.381，SE=0.170，p=0.025）和加权中位数方法（beta=0.419，SE=0.206，p=0.047）均显示咖啡摄入与骨关节炎之间存在因果关系的证据。MR-Egger 回归表明，方向性偏倚不太可能影响结果（截距=0.064；p=0.549），但表明咖啡摄入与骨关节炎之间不存在因果关系（beta=-0.518，SE=1.270，p=0.723）。Cochran's Q 检验和漏斗图表明，基于个体变体的 IV 估计值之间没有异质性的证据。MR 分析的结果支持这样一种观察结果，即咖啡摄入与骨关节炎风险增加存在因果关系。
