Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach

The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR = 2.05 per chang...

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Bibliographic Details
Published in:Nature communications Vol. 13; no. 1; pp. 2337 - 9
Main Authors: Richardson, Tom G., Crouch, Daniel J. M., Power, Grace M., Morales-Berstein, Fernanda, Hazelwood, Emma, Fang, Si, Cho, Yoonsu, Inshaw, Jamie R. J., Robertson, Catherine C., Sidore, Carlo, Cucca, Francesco, Rich, Steven S., Todd, John A., Davey Smith, George
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 28.04.2022
Nature Publishing Group
Nature Portfolio
Subjects:
45/43
692/308/174
692/308/3187
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692/699/249/1313/1418
Adult
Asthma
Body Size
Body weight
Child
Childhood
Children
Diabetes
Diabetes mellitus (insulin dependent)
Diabetes Mellitus, Type 1 - epidemiology
Diabetes Mellitus, Type 1 - genetics
Eczema
Health risks
Humanities and Social Sciences
Humans
Hypothyroidism
Infant, Newborn
Mendelian Randomization Analysis
multidisciplinary
Obesity
Overweight
Overweight - complications
Pediatric Obesity - complications
Pediatric Obesity - epidemiology
Pediatric Obesity - genetics
Randomization
Risk
Science
Science (multidisciplinary)
Skin diseases
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:The rising prevalence of childhood obesity has been postulated as an explanation for the increasing rate of individuals diagnosed with type 1 diabetes (T1D). In this study, we use Mendelian randomization (MR) to provide evidence that childhood body size has an effect on T1D risk (OR = 2.05 per change in body size category, 95% CI = 1.20 to 3.50, P = 0.008), which remains after accounting for body size at birth and during adulthood using multivariable MR (OR = 2.32, 95% CI = 1.21 to 4.42, P = 0.013). We validate this direct effect of childhood body size using data from a large-scale T1D meta-analysis based on n = 15,573 cases and n = 158,408 controls (OR = 1.94, 95% CI = 1.21 to 3.12, P = 0.006). We also provide evidence that childhood body size influences risk of asthma, eczema and hypothyroidism, although multivariable MR suggested that these effects are mediated by body size in later life. Our findings support a causal role for higher childhood body size on risk of being diagnosed with T1D, whereas its influence on the other immune-associated diseases is likely explained by a long-term effect of remaining overweight for many years over the lifecourse. The rise in type 1 diabetes is thought to be related to increased childhood obesity, but this relationship is not well understood. In this study, the authors utilize Mendelian randomization to separate the direct and indirect effects of childhood body size on risk of type 1 diabetes and 7 other immune-associated disease outcomes.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-29932-y