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Pediatrics

Causal relationships between adiposity and childhood asthma: bi-directional Mendelian Randomization analysis

Subjects

Abstract

Background/objectives

Obesity and asthma are common chronic diseases and have been reported to be mutually causative. We investigated the causal direction of the relationship between adiposity and asthma using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis.

Subjects/methods

We used data from the Taiwan Children Health Study with 24 body mass index (BMI)-single-nucleotide polymorphisms (SNPs, combined into a weighted allelic score) and 16 asthma-SNPs (combined into two weighted allelic scores, separately for asthma inflammatory and antioxidative genes) to yield genetic IVs for adiposity and asthma, respectively.

Results

The weighted allele score for BMI was strongly associated with adiposity (p = 2 × 10–16) and active asthma (p = 0.03). The two-stage least square regression risk ratio (RR) for the effect of BMI on asthma was 1.04 (95% confidence interval: 1.00–1.07, p = 0.03). Although the weighted asthma genetic scores were significantly associated with asthma (p = 8.4 × 10–3), no association was seen for genetically instrumented asthma with BMI using MR. Central obesity was the most accurate predictor of asthma. Adiposity showed higher causal effects on asthma in boys and children with non-atopic asthma. Sensitivity analysis for MR revealed no directional genetic pleiotropy effects. The causal effect RRs of BMI on asthma were 1.04, 1.08, and 1.03 for inverse-variance weighted, MR–Egger regression (slope), and weighted median methods, respectively, all in accordance with the MR estimates.

Conclusions

High adiposity may lead to asthma, whereas the effects of asthma on adiposity accumulation are likely to be small.

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Acknowledgements

The authors thank the field workers, teachers, and other school staff who supported data collection, and all parents and children who participated in this study. We also thank Ministry of Science and Technology (#101–2314-B-532–002-MY3 and #104–2314-B-532–002-MY3) and National Health Research Institutes (NHRI-EX107-10718PC) in Taiwan for grant support of this study. We thank the National Center for Genome Medicine (NCGM) for the genotyping technical support.

Author contributions

Y-CC contributed the cohort data collection, interpretation of data, and writing. H-YF and Y-TH assisted in the critical part of the statistical analysis, data interpretation, and revised it critically for important intellectual content. S-YH and T-HL contributed to analysis and interpretation of data, critically revising this manuscript for intellectual content. YL reviewed the study design, acquisition of data, interpretation of data, supervised the study, and revised the manuscript critically for important intellectual content. All authors approved the final manuscript as submitted and published, and agreed to be accountable for all aspects of the work.

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Correspondence to Yungling L. Lee.

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Chen, YC., Fan, HY., Huang, YT. et al. Causal relationships between adiposity and childhood asthma: bi-directional Mendelian Randomization analysis. Int J Obes 43, 73–81 (2019). https://doi.org/10.1038/s41366-018-0160-8

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