Summary
This Mendelian randomisation study used genetic variation as a natural experiment to disentangle the causal effects of early life body size from those of adult body size on disease risk. Whilst larger childhood body size showed associations with coronary artery disease and type 2 diabetes in univariable analyses, multivariable analysis found little evidence of direct causal effects independent of adult body size for these outcomes. However, larger early life body size demonstrated a protective direct effect on breast cancer risk independent of adult adiposity, and age at menarche showed strong independent protective effects against breast cancer.
UK applicability
The findings are directly applicable to UK public health policy, as the study was conducted using UK Biobank data. The results suggest that interventions targeting adult body weight may be particularly important for preventing coronary artery disease and type 2 diabetes, though the protective association of larger childhood body size with breast cancer warrants further investigation in UK population contexts.
Key measures
Genetically predicted body mass index in adulthood (mean age 56.5 years) and self-reported perceived body size at age 10; odds ratios for coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer
Outcomes reported
The study evaluated whether body size in early life has an independent causal effect on risk of coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer in later life, or whether its influence is mediated through adult body size. Mendelian randomisation analyses were used to distinguish direct effects from mediated effects through adult adiposity.
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