Background: It is well established that genetics, environment, and interplay between them play a crucial role in adult disease. We aimed to evaluate the role of genetics, early life nutrition, and the interaction between them, on optimal adult health. Methods: As part of a large international consortium (n~154,000), we identified 60 SNPs associated with both birthweight and adult disease. Utilising the Raine Study, we developed a birthweight polygenic score (BW-PGS) based on the 60 SNPs and

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... ined relationships between BW-PGS and adulthood cardiovascular risk factors, specifically evaluating interactions with early life nutrition. Findings: Healthy nutrition was beneficial for all individuals; longer duration of any breastfeeding was particularly associated with lower BMI and lower Systolic Blood Pressure in those with higher BW-PGS. Interpretation: Optimal breastfeeding offers the greatest benefit to reduce adult obesity and hypertension in those genetically predisposed to high birthweight. This provides an example of how precision medicine in early life can improve adult health.