Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study

Summary

OBJECTIVE: To evaluate whether body size in early life has an independent effect on risk of disease in later life or whether its influence is mediated by body size in adulthood. DESIGN: Two sample univariable and multivariable mendelian randomisation. SETTING: The UK Biobank prospective cohort study and four large scale genome-wide association studies (GWAS) consortiums. PARTICIPANTS: 453 169 participants enrolled in UK Biobank and a combined total of more than 700 000 people from different GWAS consortiums. EXPOSURES: Measured body mass index during adulthood (mean age 56.5) and self-reported perceived body size at age 10. MAIN OUTCOME MEASURES: Coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer. RESULTS: Having a larger genetically predicted body size in early l