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儿童体重指数与中耳积液风险之间的因果关系:一项孟德尔随机化研究

Causal Relationship Between Body Mass Index and Risk of Otitis Media with Effusion in Children: A Mendelian Randomization Study.

作者信息

Cao Jingwen, Liu Wei, Yang Zixuan, Qu Gaoya, Zhong Cuiping

机构信息

Otolaryngology Head and Neck Surgery, The 940th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Lanzhou, China.

Ningxia Medical University, Yinchuan, China.

出版信息

Indian J Otolaryngol Head Neck Surg. 2024 Feb;76(1):1410-1418. doi: 10.1007/s12070-023-04161-x. Epub 2023 Aug 31.

Abstract

BACKGROUND

Body mass index(BMI) in children appears to be associated with Otitis media with effusion(OME) in observational studies, but the causal relationship is not clear.

METHODS

A two-sample Mendelian randomization (MR) study was used to explore the causal relationship between childhood BMI and OME in people of European ancestry. Genome-wide association studies (GWAS) of childhood BMI were used as exposures (n = 61,111), while GWAS of OME were used as outcomes (n = 429,290). The weighted inverse variance method (IVW) was used as a baseline method to test for causality. In addition, MR-Egger, simple mode analysis, weighted median, and weighted mode were used as complementary methods.MR-PRESSO analysis, MR-Egger intercept analysis, and Cochran's Q statistical analysis were also used to detect possible directional heterogeneity and polymorphism. To assess this association, we used ratios (OR) with 95% confidence intervals (ci). All statistical analyses were performed in R.

RESULTS

We selected 22 genome-wide significant single nucleotide polymorphisms (SNPs) from GWAS as instrumental variables (IVW). the IVW approach showed evidence supporting a causal relationship between BMI and OME in children (β = 0.265, SE = 0.113, P = 0.018). MR-Egger regression showed that targeted polymorphisms were unlikely to bias the results bias (intercept=-0.022; P = 0.488), but there was no causal relationship between BMI and OME (β = 0.584, SE = 0.465, P = 0.224). Although the results of the IVW and MR Egger analyses were not consistent, the IVW analysis maintained higher precision, and the Cochran Q test, heterogeneity and polymorphism tests showed no heterogeneity, no directionality and no polymorphism.

CONCLUSIONS

MR studies suggest that genetically predicted body mass index in childhood is associated with an increased risk of OME. Notably, given the limitations of this study, the mechanism of association between body mass index and OME in childhood needs further investigation. These results support the importance of effective management of obesity, which may reduce OME occurrence and decrease OME recurrence.

摘要

背景

在观察性研究中,儿童的体重指数(BMI)似乎与中耳积液性中耳炎(OME)相关,但因果关系尚不清楚。

方法

采用两样本孟德尔随机化(MR)研究来探讨欧洲血统人群中儿童BMI与OME之间的因果关系。儿童BMI的全基因组关联研究(GWAS)用作暴露因素(n = 61,111),而OME的GWAS用作结局(n = 429,290)。加权逆方差法(IVW)用作检验因果关系的基线方法。此外,MR-Egger、简单模式分析、加权中位数和加权模式用作补充方法。还使用MR-PRESSO分析、MR-Egger截距分析和 Cochr an Q统计分析来检测可能的方向异质性和多态性。为评估这种关联,我们使用了比值比(OR)及95%置信区间(ci)。所有统计分析均在R中进行。

结果

我们从GWAS中选择了22个全基因组显著的单核苷酸多态性(SNP)作为工具变量(IVW)。IVW方法显示有证据支持儿童BMI与OME之间存在因果关系(β = 0.265,SE = 0.113,P = 0.018)。MR-Egger回归表明目标多态性不太可能导致结果偏差(截距 = -0.022;P = 0.488),但BMI与OME之间不存在因果关系(β = 0.584,SE = 0.465,P = 0.224)。尽管IVW和MR Egger分析的结果不一致,但IVW分析保持了更高的精度,Cochran Q检验、异质性和多态性检验均未显示异质性、方向性和多态性。

结论

MR研究表明,儿童期遗传预测的体重指数与OME风险增加相关。值得注意的是,鉴于本研究的局限性,儿童期体重指数与OME之间的关联机制需要进一步研究。这些结果支持了有效管理肥胖的重要性,这可能会减少OME的发生并降低OME的复发率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5da/10909010/4d74ff2b9d30/12070_2023_4161_Fig1_HTML.jpg

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