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Causal Relationship Between Body Mass Index and Risk of Otitis Media with Effusion in Children: A Mendelian
Jingwen Cao1,2, Wei Liu2,3, Zixuan Yang2
1Otolaryngology Head and Neck Surgery, The 940th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Lanzhou, China.
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.
Insights
Genetically predicted childhood body mass index (BMI) is linked to a higher risk of otitis media with effusion (OME). Managing childhood obesity may help reduce OME incidence and recurrence.
Area of Science:
- Genetics
- Pediatrics
- Epidemiology
Background:
- Observational studies suggest a link between childhood body mass index (BMI) and otitis media with effusion (OME).
- The causal relationship between childhood BMI and OME remains unclear.
- Further investigation is needed to understand the association between childhood BMI and OME.
Purpose of the Study:
- To investigate the causal relationship between childhood BMI and OME using a two-sample Mendelian randomization (MR) study.
- To leverage genome-wide association studies (GWAS) for both childhood BMI and OME in a European ancestry population.
- To assess the potential causal effect of genetically predicted childhood BMI on OME risk.
Main Methods:
- Employed a two-sample Mendelian randomization (MR) design.
- Utilized GWAS data for childhood BMI (exposures) and OME (outcomes).
- Applied various statistical methods including Inverse Variance Weighted (IVW), MR-Egger, and heterogeneity/pleiotropy tests.
Main Results:
- The IVW method indicated a causal relationship between childhood BMI and OME (P=0.018).
- MR-Egger regression did not find a significant causal relationship (P=0.224), suggesting potential pleiotropy or other biases.
- Heterogeneity and pleiotropy tests did not reveal significant issues, supporting the IVW findings despite inconsistencies.
Conclusions:
- Mendelian randomization suggests genetically predicted childhood BMI is associated with increased OME risk.
- Effective management of childhood obesity may be crucial for reducing OME occurrence and recurrence.
- Further research is warranted to elucidate the underlying mechanisms connecting childhood BMI and OME.
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Observational studies are those where the researcher does not intervene but rather observes natural variations. They include cross-sectional, cohort, and...