Here, we use recently developed computational algorithms and large datasets to derive, validate and test a robust polygenic predictor of BMI and obesity. This genome-wide polygenic score (GPS) integrates all available common variants into a single quantitative measure of inherited susceptibility. It identifies a subset of the adult population that is at substantial risk of severe obesity – in some cases equivalent to rare monogenic mutations – and others that enjoy considerable protection. The GPS is associated with only minimal differences in birthweight, but it predicts clear differences in weight during early childhood and profound differences in weight trajectory and risk of developing severe obesity in subsequent years.
