Childhood Asthma and Type 1 Diabetes Mellitus: A Meta-analysis and
Bidirectional Mendelian Randomization Study
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.