目的:腹疝(AH)是临床最常见的疾病之一。大量观察性研究发现,肥胖是AH的重要危险因素。然而,肥胖与AH之间的因果关系无法确定,因为关于肥胖诱发AH的临床研究相对较少,并且只有一些小型或中型观察性研究。观察性研究由于其缺点而具有许多混杂因素和反向因果关系。从循证医学的角度来看,他们没有足够的说服力。因此,仍然缺乏高质量的,基于证据的医学证据支持肥胖和AH之间的因果关系。肥胖和AH之间的因果关系也几乎不可能通过随机对照试验(RCTs)证实。我们基于孟德尔随机化(MR)的研究可能为肥胖与AH之间的关系提供更高水平的循证医学支持。体重指数(BMI)是用于定义肥胖的最常用指标。最后,我们采用双样本孟德尔随机化(TSMR)来探讨BMI与AH之间的因果关系.
方法:AH相关的单核苷酸多态性(SNP)数据来自FinnGen生物库(FB),和BMI相关的单核苷酸多态性(SNP)数据从英国生物库(UKB)获得。遗传基因座被用作工具变量(IVs),采用方差逆加权(IVW)等方法进行双样本孟德尔随机化分析,用比值比(OR)值评价BMI与AH之间的因果关系。
结果:通过Egger截距法计算水平多效性测试的结果:p=0.34>0.05。MR-Egger法和IVW法的CochranQ检验显示异质性P=0.03<0.05,因此以IVW随机效应模型为金标准。我们发现,遗传确定的BMI的1-标准差(SD)增量会增加AH的66.0%风险(N=371SNP,OR=1.66,95%CI1.46-1.89,p=1.55E-14)基于IVW随机效应模型,该模型与其他七种方法的结果几乎一致。
结论:我们的MR发现了BMI和AH的遗传证据。发生AH的风险随着BMI的增加而增加。这一发现提供了进一步的证据,表明保持健康的BMI可以预防AH的发展。此外,临床医生可能需要关注一些高BMI患者AH的潜在风险.
Abdominal hernia (AH) is one of the most common clinical diseases. A large number of observational studies have found that obesity is an important risk factor for AH. However, the causal relationship between obesity and AH cannot be determined because of the clinical studies on AH induced by obesity are relatively few and only have some small- or medium-scale observational studies. Observational studies have so many confounding factors and reverse causality due to their shortcomings. From an evidence-based medicine perspective, they are not sufficiently convincing. Therefore, there is still a lack of high-quality, evidence-based medical evidence supporting a causal relationship between obesity and AH. A causal relationship between obesity and AH is also almost impossible to confirm by randomized controlled trials (RCTs). Our study based on Mendelian randomization (MR) may provide a higher level of evidence-based medical support for the relationship between obesity and AH. Body mass index (BMI) is the most common measure used for defining obesity. Finally, we employed two-sample Mendelian randomization (TSMR) to explore the causal relationship between BMI and AH.
AH-related single nucleotide polymorphisms (SNPs) data were obtained from the FinnGen Biobank (FB), and BMI-related single nucleotide polymorphisms (SNPs) data were obtained from the UK Biobank (UKB). Genetic loci are used as instrumental variables (IVs), methods such as inverse variance weighted (IVW) were used for two-sample Mendelian randomization analysis, and the odds ratio (OR) value was used to evaluate the causal relationship between BMI and AH.
The results of the horizontal pleiotropy test were calculated by Egger-intercept method: p = 0.34 > 0.05. The Cochran Q test of MR-Egger method and IVW method showed heterogeneity P = 0.03 < 0.05, so the IVW random effect model was used as the gold standard. We found a genetically determined 1-standard deviation (SD) increment of BMI causally increased a 66.0% risk of AH (N = 371 SNPs, OR = 1.66, 95% CI 1.46-1.89, p = 1.55E-14) based on the IVW random effect model which was almost consistent with the results of other seven methods.
Our MR found genetic evidence for BMI and AH. The risk of developing AH increases with the number of BMI. This finding provides further evidence that maintaining a healthy BMI can prevent the development of AH. In addition, clinicians may need to focus on the potential risk of AH on some high-BMI patients.