Data from: Childhood adiposity and type 1 diabetes: a Mendelian randomization study

BACKGROUND: The incidence of type 1 diabetes (T1D) is increasing globally.
One hypothesis is that increasing childhood obesity rates may explain part
of this increase, but, as T1D is rare, intervention studies are
challenging to perform. The aim of this study was to assess this
hypothesis with a Mendelian randomization approach that uses genetic
variants as instrumental variables to test for causal associations.
METHODS AND FINDINGS: We created a genetic instrument of 23 single
nucleotide polymorphisms (SNPs) associated with childhood adiposity in
children aged 2-10 years. Summary-level association results for these 23
SNPs with childhood-onset (<17 years) T1D were extracted from a
meta-analysis of genome-wide association study with 5,913 T1D cases and
8,828 reference samples. Using inverse-variance weighted Mendelian
randomization analysis, we found support for an effect of childhood
adiposity on T1D risk (odds ratio 1.32, 95% CI 1.06-1.64 per standard
deviation score in body mass index [SDS-BMI]). A sensitivity analysis
provided evidence of horizontal pleiotropy bias (p = 0.04) diluting the
estimates towards the null. We therefore applied Egger regression and
multivariable Mendelian randomization methods to control for this type of
bias and found evidence in support of a role of childhood adiposity in T1D
(odds ratio in Egger regression, 2.76, 95% CI 1.40-5.44). Limitations of
our study include that underlying genes and their mechanisms for most of
the genetic variants included in the score are not known. Mendelian
randomization requires large sample sizes, and power was limited to
provide precise estimates. This research has been conducted using data
from the Early Growth Genetics (EGG) Consortium, the Genetic Investigation
of Anthropometric Traits (GIANT) Consortium, the Tobacco and Genetics
(TAG) Consortium, and the Social Science Genetic Association Consortium
(SSGAC), as well as meta-analysis results from a T1D genome-wide
association study. CONCLUSIONS: This study provides genetic support for a
link between childhood adiposity and T1D risk. Together with evidence from
observational studies, our findings further emphasize the importance of
measures to reduce the global epidemic of childhood obesity and encourage
mechanistic studies.