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