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

Corresponding Author:[email protected]

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Junyang Xie
First Affiliated Hospital of Guangzhou Medical University
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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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Wenjing Liao
First Affiliated Hospital of Guangzhou Medical University
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Lijuan Song
First Affiliated Hospital of Guangzhou Medical University
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Abstract

Objectives: World-wide incidence and prevalence of both asthma and type 1 diabetes mellitus (T1DM) has been increasing in past decades. Association between the two diseases has been found in some but not other studies. 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 decreased genetic risk of asthma in children with T1DM (OR = 0.937, 95%CI 0.881-0.996, P = 0.037). Conclusions: Childhood asthma is a risk factor for T1DM; T1DM is a possible protective factor for childhood asthma.