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

Tom G. Richardson (), Daniel J. M. Crouch, Grace M. Power, Fernanda Morales-Berstein, Emma Hazelwood, Si Fang, Yoonsu Cho, Jamie R. J. Inshaw, Catherine C. Robertson, Carlo Sidore, Francesco Cucca, Steven S. Rich, John A. Todd and George Davey Smith
Additional contact information
Tom G. Richardson: University of Bristol, Oakfield House, Oakfield Grove
Daniel J. M. Crouch: NIHR Biomedical Research Centre, University of Oxford
Grace M. Power: University of Bristol, Oakfield House, Oakfield Grove
Fernanda Morales-Berstein: University of Bristol, Oakfield House, Oakfield Grove
Emma Hazelwood: University of Bristol, Oakfield House, Oakfield Grove
Si Fang: University of Bristol, Oakfield House, Oakfield Grove
Yoonsu Cho: University of Bristol, Oakfield House, Oakfield Grove
Jamie R. J. Inshaw: NIHR Biomedical Research Centre, University of Oxford
Catherine C. Robertson: University of Virginia
Carlo Sidore: Institute for Research in Genetics and Biomedicine (IRGB)
Francesco Cucca: Institute for Research in Genetics and Biomedicine (IRGB)
Steven S. Rich: University of Virginia
John A. Todd: NIHR Biomedical Research Centre, University of Oxford
George Davey Smith: University of Bristol, Oakfield House, Oakfield Grove

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-29932-y

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