INTRODUCTION
Asthma is one of the most frequent chronic disease in
children.1,2 Type 1 diabetes mellitus (T1DM) occurs at
an incidence of 8-20 per 100,000 each year,3 and is
one of the most common immune-related diseases in children. The
incidence and prevalence of both childhood asthma and T1DM have been
increasing over the past decades,1,3 suggesting common
susceptibility factors.4
A meta-analysis published in 2003 suggested a weak inverse association
between childhood asthma and T1DM.5 However, majority
of the studies included in the meta-analysis are case-control studies.
In addition, cohort studies included in the meta-analysis are highly
heterogeneous in disease definition and age spectrum. In addition, a
positive association between the two diseases , which now attracts
growing interest, has also been reported in several retrospective cohort
studies with stronger quality of evidence.6-8
Since exaggerated immune response and inflammation underlie both asthma
and T1DM, reciprocal cause-effect relationship between the two diseases
is likely. Mendelian randomization (MR) analysis uses genetic variants
as instrumental variables (IVs) for investigating potential cause-effect
relationships between different human traits.9 With
increasing number of genome-wide association studies (GWAS), MR has been
increasingly used. Bidirectional MR analysis is an extension to the
basic MR approach that could evaluate whether an “exposure” causes the
“outcome” or vice versa.10 We conducted an updated
meta-analysis of original studies that examined the association between
childhood asthma and T1DM. Data were analyzed using bidirectional MR
analysis to examine the possible cause-effect relationship.