Department of Orthopedic Surgery, Tangdu Hospital, Fourth Military Medical University, No. 1 of Xinsi Road, Baqiao District, 710038, Xi'an City, Shaanxi Province, China.
Department of Orthopedic Surgery, The Fourth People's Hospital of Zibo, No. 210 of Shanquan Road, Zhangdian District, 255051, Shandong, Shandong Province, China.
BMC Med Genomics. 2023 Mar 3;16(1):41. doi: 10.1186/s12920-023-01461-7.
Previous observational studies have shown an association between asthma, atopic dermatitis (AD) and rheumatoid arthritis (RA). However, the bidirectional cause-effect chain between asthma and AD and RA has not been proven yet.
We performed bidirectional two-sample Mendelian randomization (TSMR) and selected single nucleotide polymorphisms (SNPs) associated with asthma, AD, and RA as instrumental variables. All of the SNPs were obtained from the latest genome-wide association study in Europeans. Inverse variance weighted (IVW) was the main method used in MR analysis. MR-Egger, weighted model, simple model, and weighted median were used for quality control. The robustness of the results was tested by sensitivity analysis.
Asthma was found to be the largest effect size for RA susceptibility using the IVW method (OR, 1.35;95%CI, 1.13-1.60; P, 0.001), followed by AD (OR, 1.10;95%CI, 1.02-1.19; P, 0.019). In contrast, there was no causal relationship between RA and asthma (IVW: P = 0.673) or AD (IVW: P = 0.342). No pleiotropy or heterogeneity was found in the sensitivity analysis.
Findings from this study showed a causal relationship between genetic susceptibility to asthma or AD and increased risk of RA, but do not support a causal relationship between genetic susceptibility to RA and asthma or AD.
先前的观察性研究表明，哮喘、特应性皮炎（AD）和类风湿关节炎（RA）之间存在关联。然而，哮喘和 AD 与 RA 之间的双向因果关系尚未得到证实。
我们进行了双向两样本孟德尔随机化（TSMR），并选择与哮喘、AD 和 RA 相关的单核苷酸多态性（SNP）作为工具变量。所有 SNP 均来自欧洲最新的全基因组关联研究。反向方差加权（IVW）是 MR 分析的主要方法。MR-Egger、加权模型、简单模型和加权中位数用于质量控制。通过敏感性分析测试结果的稳健性。
使用 IVW 方法发现哮喘对 RA 易感性的影响最大（OR，1.35；95%CI，1.13-1.60；P，0.001），其次是 AD（OR，1.10；95%CI，1.02-1.19；P，0.019）。相比之下，RA 与哮喘（IVW：P = 0.673）或 AD（IVW：P = 0.342）之间没有因果关系。敏感性分析未发现多效性或异质性。
本研究结果表明，哮喘或 AD 的遗传易感性与 RA 风险增加之间存在因果关系，但不支持 RA 的遗传易感性与哮喘或 AD 之间存在因果关系。
