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孟德尔随机化表明特应性皮炎会导致糖尿病的发生。

Mendelian randomization indicates that atopic dermatitis contributes to the occurrence of diabetes.

机构信息

Department of Echocardiography, Zhongshan Hospital Fudan University, Shanghai, 200032, China.

Department of Transfusion, Zhongshan Hospital Fudan University, Shanghai, 200032, China.

出版信息

BMC Med Genomics. 2023 Jun 15;16(1):132. doi: 10.1186/s12920-023-01575-y.

Abstract

BACKGROUND

An association has been indicated between atopic dermatitis (AD), a prevalent chronic inflammatory skin disease, and diabetes mellitus. However, the exact causal relationship between AD and both type 1 diabetes (T1D) and type 2 diabetes (T2D) remains controversial. This study aimed to explore the causal association between AD and diabetes by Mendelian Randomization (MR) approaches.

METHODS

Public genetic summary data for AD was obtained from EAGLE study. Single nucleotide polymorphisms of diabetes were retrieved from four genome-wide association studies that had been performed in European populations. Inverse variance weighted (IVW) in MR analysis was used as the primary means of causality estimation. Several complementary analyses and sensitivity analyses were performed to calculate MR estimates and to enhance the causal inference, respectively. The R package 'TwoSampleMR' was used for analysis.

RESULTS

Genetically predicted AD led to a higher risk of T1D (OR, 1.19; 95% CI, 1.05, 1.34; P = 0.006) and T2D (OR, 1.07; 95% CI, 1.02, 1.11; P = 0.003) based on random-effect IVW method. The complementary analyses provided similar positive results. Cochran's Q test and I statistics indicated moderate heterogeneity between AD and both T1D and T2D. No significant horizontal pleiotropy was detected by MR-Egger Intercept p except summary data from FinnGen consortium.

CONCLUSION

Genetically predicted AD is a risk factor for both T1D and T2D. These findings imply potential shared pathological mechanisms between AD and diabetes, thus suggesting the significance of early clinical diagnosis and prevention of AD in reducing the incidence of diabetes.

摘要

背景

特应性皮炎(AD)是一种常见的慢性炎症性皮肤病,与糖尿病之间存在关联。然而,AD 与 1 型糖尿病(T1D)和 2 型糖尿病(T2D)之间的确切因果关系仍存在争议。本研究旨在通过孟德尔随机化(MR)方法探讨 AD 与糖尿病之间的因果关系。

方法

从 EAGLE 研究中获取 AD 的公共遗传汇总数据。从四项在欧洲人群中进行的全基因组关联研究中检索到糖尿病的单核苷酸多态性。MR 分析中使用逆方差加权(IVW)作为因果估计的主要方法。分别进行了几种补充分析和敏感性分析,以计算 MR 估计值并增强因果推断。使用 R 包 'TwoSampleMR' 进行分析。

结果

基于随机效应 IVW 方法,遗传预测的 AD 导致 T1D(OR,1.19;95%CI,1.05,1.34;P=0.006)和 T2D(OR,1.07;95%CI,1.02,1.11;P=0.003)的风险增加。补充分析提供了类似的阳性结果。Cochran's Q 检验和 I 统计量表明 AD 与 T1D 和 T2D 之间存在中度异质性。除了 FinnGen 联盟的汇总数据外,MR-Egger 截距 p 未检测到显著的水平偏倚。

结论

遗传预测的 AD 是 T1D 和 T2D 的危险因素。这些发现表明 AD 和糖尿病之间可能存在共同的病理机制,因此提示早期临床诊断和预防 AD 对于降低糖尿病的发病率具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ece4/10268454/952ce281e3fe/12920_2023_1575_Fig1_HTML.jpg

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