Zhou Weixin, Cai Jie, Li Zifan, Lin Ying
The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Dermatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
J Eur Acad Dermatol Venereol. 2023 Mar 15. doi: 10.1111/jdv.19048.
Observational studies have suggested associations of atopic dermatitis (AD) with conjunctivitis and other ocular surface diseases (OSDs). It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded.
Our study aims to examine the causal association of AD with conjunctivitis and other OSDs.
A bidirectional two-sample Mendelian randomization (MR) study was performed with genome-wide association study (GWAS) summary-level statistics. Genetic instruments for AD from a GWAS meta-analysis study conducted by the EArly Genetics & Lifecourse Epidemiology eczema consortium were used to investigate AD's relationships to conjunctivitis and other OSDs among cases from the FinnGen consortium. Genetic correlations were calculated using linkage disequilibrium score regression. Causal estimates were derived by the inverse-variance weighted method and were verified through a series of sensitivity analyses.
Genetically predicted AD linked to higher risk of conjunctivitis (OR, 1.48; 95% CI, 1.33-1.65; p = 8.65 × 10 ) and allergic conjunctivitis (OR, 1.53; 95%CI, 1.31-1.77; p = 3.77 × 10 ), as well as atopic conjunctivitis (OR, 1.76; 95%CI, 1.24-2.52; p = 1.76 × 10 ). Additionally, suggestive causal effects of AD on chronic conjunctivitis (OR, 1.76; 95%CI, 1.24-2.52; p = 5.78 × 10 ) and keratitis (OR, 1.14; 95%CI, 1.01-1.30; p = 3.58 × 10 ) were found. No significant causal effect of AD was identified in relation to keratitis, keratoconus and pterygium. Concerning the reverse directions, no significant associations were noted.
Findings of this MR study support a causal effect between AD and conjunctivitis, but not vice versa. These findings have clinical implications for the management of AD and conjunctivitis.
观察性研究表明特应性皮炎（AD）与结膜炎及其他眼表疾病（OSD）之间存在关联。然而，因果关系是否存在以及方向如何仍不明确，因为这些关联可能存在混杂因素。
我们的研究旨在检验AD与结膜炎及其他OSD之间的因果关联。
采用全基因组关联研究（GWAS）汇总水平统计数据进行双向双样本孟德尔随机化（MR）研究。使用早期遗传学与生命历程流行病学湿疹联盟进行的GWAS荟萃分析研究中AD的遗传工具，来调查芬兰基因组联盟病例中AD与结膜炎及其他OSD的关系。使用连锁不平衡评分回归计算遗传相关性。通过逆方差加权法得出因果估计值，并通过一系列敏感性分析进行验证。
遗传预测的AD与结膜炎（比值比[OR]，1.48；95%置信区间[CI]，1.33 - 1.65；p = 8.65×10 ）、过敏性结膜炎（OR，1.53；95%CI，1.31 - 1.77；p = 3.77×10 ）以及特应性结膜炎（OR，1.76；95%CI，1.24 - 2.52；p = 1.76×10 ）的较高风险相关。此外，还发现AD对慢性结膜炎（OR，1.76；95%CI，1.24 - 2.52；p = 5.78×10 ）和角膜炎（OR，1.14；95%CI，1.01 - 1.30；p = 3.58×10 ）有提示性因果效应。未发现AD与角膜炎、圆锥角膜和翼状胬肉有显著因果效应。关于反向关系，未发现显著关联。
这项MR研究的结果支持AD与结膜炎之间存在因果效应，但反之则不然。这些发现对AD和结膜炎的管理具有临床意义。
