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Childhood Asthma and Type 1 Diabetes Mellitus: A Meta-analysis and Bidirectional Mendelian Randomization Study
  • +9
  • Junyang Xie,
  • Gui Chen,
  • Tianhao Liang,
  • Ang Li,
  • Weixing Liu,
  • Yiyan Wang,
  • Xiaofen Wang,
  • Xiaoxuan Kuang,
  • Demin Han,
  • Wenjing Liao,
  • Lijuan Song,
  • Xiaowen Zhang
Junyang Xie
First Affiliated Hospital of Guangzhou Medical University

Corresponding Author:entjunyang@163.com

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Gui Chen
First Affiliated Hospital of Guangzhou Medical University
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Tianhao Liang
First Affiliated Hospital of Guangzhou Medical University
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Ang Li
First Affiliated Hospital of Guangzhou Medical University
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Weixing Liu
First Affiliated Hospital of Guangzhou Medical University
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Yiyan Wang
First Affiliated Hospital of Guangzhou Medical University
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Xiaofen Wang
First Affiliated Hospital of Guangzhou Medical University
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Xiaoxuan Kuang
First Affiliated Hospital of Guangzhou Medical University
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Demin Han
First Affiliated Hospital of Guangzhou Medical University
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Wenjing Liao
First Affiliated Hospital, Guangzhou Medical University
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Lijuan Song
First Affiliated Hospital of Guangzhou Medical University
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Xiaowen Zhang
the First Affiliated Hospital, Guangzhou Medical College.
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Abstract

Background: World-wide incidence and prevalence of both asthma and type 1 diabetes mellitus (T1DM) in children has been increasing in past decades. Association between the two diseases has been found in some but not other studies. Objective: We conducted a meta-analysis to verify such an association, and bidirectional Mendelian randomization analysis to examine the potential cause-effect relationships. Methods: Three databases (PubMed, Embase and Web of Science) were searched from their inception to February 1, 2021. Pooled hazard ratios (HR) or odds ratios (OR), and 95% confidence intervals, were calculated. Associations between single-nucleotide polymorphisms with childhood asthma and T1DM were selected based on genome-wide association studies. The outcome datasets were obtained from FinnGen study. We used the inverse variance-weighted, weighted median and MR-Egger methods to estimate causal effects. To assess robustness and horizontal pleiotropy, MR-Egger regression and MR pleiotropy residual sum and outlier test was conducted. Results: In meta-analysis, childhood asthma was associated with an increased risk of T1DM (HR=1.30, 95% CI 1.05-1.61, P=0.014), whereas T1DM was not associated with the risk of asthma (HR=0.98, 95% CI 0.64-1.51, P=0.941; OR=0.84, 95% CI 0.65-1.08, P=0.168). MR analysis indicated increased genetic risk of T1DM in children with asthma (OR=1.308; 95% CI 1.030-1.661; P =0.028). Analysis using the IVW method indicated not associated between T1DM and genetic risk of asthma (OR=1.027, 95%CI 0.970-1.089, P=0.358). Conclusion: Both meta-analysis and MR study suggested that childhood asthma was a risk factor for T1DM. No epidemiological or genetic evidence for an association of T1DM with asthma incidence. Further studies could be carried out to leverage this newfound insight into better clinical and experimental research in asthma and T1DM. Further studies could be carried out to leverage this newfound insight into better clinical and experimental research in asthma and T1DM.
14 Mar 2022Submitted to Pediatric Allergy and Immunology
22 Mar 2022Reviewer(s) Assigned
28 Apr 2022Review(s) Completed, Editorial Evaluation Pending
19 May 2022Editorial Decision: Revise Major
05 Aug 20221st Revision Received
08 Aug 2022Review(s) Completed, Editorial Evaluation Pending
09 Aug 2022Reviewer(s) Assigned
06 Sep 2022Editorial Decision: Accept
Sep 2022Published in Pediatric Allergy and Immunology volume 33 issue 9. 10.1111/pai.13858